Name: 14062-18-1|Ethyl 2-(4-methoxyphenyl)acetate|98%
Brand: Ambeed
SKU: A754029
Price: 8.0 USD
Availability: InStock
Rating: 98 (40 reviews)

1
[ 104-01-8 ]
[ 64-17-5 ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
99%	With toluene-4-sulfonic acid for 2h; Reflux; Inert atmosphere;
97%	With acetyl chloride at 50℃; for 1.5h;
96%	With hydrogenchloride for 20h;

96%	With hydrogenchloride Heating;
95%	With bismuth(lll) trifluoromethanesulfonate for 6h; Reflux;
89%	for 5h; Heating / reflux;	1.1D.4A To a solution of 4-methoxyphenylacetic acid (98 g, 590 mmol), in absolute ethanol (300 mL), was added of p-toluenesulfonic acid (20 g, 105 mmol). The reaction mixture was heated to reflux and maintained at that temperature for 5 hours then cooled to room temperature and concentrated to dryness. The resulting oil was purified by flash chromatography (silica gel, 20% ethyl acetate/hexanes) to give 102 g (89%) of the above-identified product as a colorless oil: 1H-NMR (d, DMSO) 1.17 (t, J=8.7 Hz, 3H), 3.56 (s, 2H), 3.73 (s, 3H), 4.05 (q, J=7.2 Hz, 2H), 6.87 (d, J=8.7 Hz, 2H), 7 17 (d, 8.7 Hz, 2H); MS (ion spray) 195.3 (M+1); Anal. Calc'd for C11H14O3: C, 68.02; H, 7.27. Found: C, 67.95, 7.17.
87%	With sulfuric acid for 18h; Heating;
87%	With toluene-4-sulfonic acid In benzene for 10h; Heating;
86%	Stage #1: 4-Methoxyphenylacetic acid With thionyl chloride In dichloromethane at 0℃; for 0.25h; Stage #2: ethanol In dichloromethane at 0℃; for 2h; Stage #3: With triethylamine In dichloromethane at 0 - 20℃; for 8h;
85%	With graphene oxide at 100℃; for 24h;	General procedure for the synthesis of esters from acids and alcohols General procedure: A mixture of acid (0.2 mmol), alcohol (0.6 mmol) and GO (50 wt%, calculated with the mass of acid) in ethyl alcohol or DCE (1 mL) was placed in a test tube equipped with a magnetic stirring bar. The mixture was stirred at 100 °C for 24 h. After the reaction was finished, filtered the GO, solvent was removed, and the residue was separated by column chromatography to give the pure sample.
	With sulfuric acid
	With sulfuric acid
	With hydrogen cation
	Heating / reflux;	7 2. Synthesis of carboxylic acid intermediates; General procedure for synthesis of compounds 10 to 16; The appropriate phenyl acetic acid 10 was dissolved in anhydrous ethanol and refluxed in the presence of a catalytic amount of sulfuric acid to produce the ethyl ester 11. The ethyl ester was then refluxed in chloroform for 24 h using an equimolar amount of freshly recrystallised λ/-bromosuccinimide and a catalytic quantity of benzoyl peroxide to produce the α-bromo-arylester 12. The pyrrole 14 was produced by refluxing of the appropriate aminophenol (or may be prepared from an aminopyridinol) 13 in glacial acetic acid for 4 h using a molar equivalent of 2,5-dimethyoxytetrahydrofuran (mixture of cis- and trans- isomers). The pyrrole 14 was then deprotonated at the hydroxyl position by use of sodium hydride in dry tetrahydrofuran (THF) at 0 0C for 1 h followed by coupling an equimolar quantity of the ς-bromo-arylester 12 in dry THF overnight to produce the ethylester-acetamide 15. Hydrolysis of the ethyl ester 15 to the corresponding acid 16 was achieved using a 10% sodium hydroxide solution in ethanol/THF (1 :1 ), stirring at room temperature for 2 h.(4-Methoxy-phenyl)-(2-pyrrol-1-yl-pyridin-3-yloxy)-acetic acid (16a); MS-ESI: m/z 325.1 (99%, M+1 ). 1H-NMR (CD3OD) δ 3.84 (3H, s), 5.89 (1H, s), 6.31 (2H, t, J=2A Hz), 6.96 (2H, d, J=9 Hz), 7.22 (1 H, q), 7.50 (2H, d, J=9 Hz), 7.57 (1 H, d), 7.74 (2H, t, J=2.4 Hz), 8.06 (1 H, dd).
	With acetyl chloride at 50℃; for 1h; Inert atmosphere;
2.14 g	for 2h; Heating / reflux;
	With sulfuric acid In benzene Reflux;
	With sulfuric acid In benzene Reflux;
	With sulfuric acid at 80℃; for 3h; Reflux; Inert atmosphere;
	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; Inert atmosphere;	4.4.3.1. Synthesis of 2-aryl-acetate esters General procedure: The corresponding alcohol (1.5 equiv) and acid (1 equiv) were dissolved in drydichloromethane (15 mL). The solution was cooled to 0 C and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) (1.5 equiv)and catalytic amounts of DMAP were added. The reaction mixture was stirred at room temperature overnight. The reaction was then diluted with water and extracted with dichloromethane(2 20 mL). The combined organic extract was dried with Na2SO4 and concentrated under reduced pressure. The desired 2-arylacetate ester product was obtained through purification by flash column chromatography using a ethyl acetate-hexanes mixture (1:4).
	With sulfuric acid
	With methanesulfonic acid
	With toluene-4-sulfonic acid for 2h; Reflux;

Reference： [1]Davis, Owen A.; Croft, Rosemary A.; Bull, James A. [Chemical Communications, 2015, vol. 51, # 84, p. 15446 - 15449]
[2]Bailey, William F.; Lambert, Kyle M.; Stempel, Zachary D.; Wiberg, Kenneth B.; Mercado, Brandon Q. [Journal of Organic Chemistry, 2016, vol. 81, # 24, p. 12116 - 12127]
[3]Katz, Christopher E.; Aube, Jeffrey [Journal of the American Chemical Society, 2003, vol. 125, # 46, p. 13948 - 13949]
[4]Matulenko, Mark A.; Paight, Ernest S.; Frey, Robin R.; Gomtsyan, Arthur; DiDomenico Jr., Stanley; Jiang, Meiqun; Lee, Chih-Hung; Stewart, Andrew O.; Yu, Haixia; Kohlhaas, Kathy L.; Alexander, Karen M.; McGaraughty, Steve; Mikusa, Joseph; Marsh, Kennan C.; Muchmore, Steven W.; Jakob, Clarissa L.; Kowaluk, Elizabeth A.; Jarvis, Michael F.; Bhagwat, Shripad S. [Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 4, p. 1586 - 1605]
[5]Location in patent: experimental part Kwie, Franciane Ho A.; Baudoin-Dehoux, Cecile; Blonski, Casimir; Lherbet, Christian [Synthetic Communications, 2010, vol. 40, # 7, p. 1082 - 1087]
[6]Current Patent Assignee: ELI LILLY & CO - US6828331, 2004, B1 Location in patent: Page column 29
[7]Taber, Douglass F.; Mack, James F.; Rheingold, Arnold L.; Geib, Steven J. [Journal of Organic Chemistry, 1989, vol. 54, # 16, p. 3831 - 3836]
[8]Lu, Xingliang; Silverman, Richard B. [Journal of the American Chemical Society, 1998, vol. 120, # 41, p. 10583 - 10587]
[9]Hu, Jundie; Guan, Mingyu; Han, Jian; Huang, Zhi-Bin; Shi, Da-Qing; Zhao, Yingsheng [Journal of Organic Chemistry, 2015, vol. 80, # 16, p. 7896 - 7904]
[10]Chen, Zhengwang; Wen, Yuelu; Fu, Yejuan; Chen, Hai; Ye, Min; Luo, Guotian [Synlett, 2017, vol. 28, # 8, p. 981 - 985]
[11]Liwschiz et al. [Zhurnal Obshchei Khimii, 1947, vol. 17, p. 1671,1675][Chem.Abstr., 1948, p. 2606] CARTER; HEY [Journal of the Chemical Society, 1948, vol. 2, p. 147 - 149]
[12]Smith,P.J.; Bourns,A.N. [Canadian Journal of Chemistry, 1974, vol. 52, p. 749 - 760]
[13]Brown,H.C.; Kim,C.J. [Journal of the American Chemical Society, 1968, vol. 90, p. 2082 - 2096]
[14]Tuncay, Atilla; Carroll, Margaret A.; Labeots, Laura A.; Pawlak, Joe M. [Journal of the Chemical Society. Chemical communications, 1988, # 24, p. 1590 - 1592]
[15]Current Patent Assignee: UNIVERSITY OF SYDNEY - WO2009/79683, 2009, A1 Location in patent: Page/Page column 44-46
[16]Xu, Yingju; McLaughlin, Mark; Chen, Cheng-Yi; Reamer, Robert A.; Dormer, Peter G.; Davies, Ian W. [Journal of Organic Chemistry, 2009, vol. 74, # 14, p. 5100 - 5103]
[17]Current Patent Assignee: ROCHE HOLDING AG - US6335332, 2002, B1 Location in patent: Page column 10
[18]Location in patent: scheme or table Gao, Yunlong; Zhao, Guilong; Liu, Wei; Wang, Yuli; Xu, Weiren; Wang, Jianwu [Chinese Journal of Chemistry, 2010, vol. 28, # 4, p. 605 - 612]
[19]Location in patent: experimental part Gao; Zhao; Liu; Shao; Wang; Tang; Wang [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2010, vol. 49, # 11, p. 1499 - 1508]
[20]Nguyen, Quyen; Nguyen, Tuyen; Driver, Tom G. [Journal of the American Chemical Society, 2013, vol. 135, # 2, p. 620 - 623]
[21]Tyagi, Vikas; Alwaseem, Hanan; O'Dwyer, Kristen M.; Ponder, Jessica; Li, Qi Ying; Jordan, Craig T.; Fasan, Rudi [Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 17, p. 3876 - 3886]
[22]Rostom, Sherif A.F.; Badr, Mona H.; Abd El Razik, Heba A.; Ashour, Hayam M.A. [European Journal of Medicinal Chemistry, 2017, vol. 139, p. 263 - 279]
[23]Estrada, Carl D.; Ang, Hwee Ting; Vetter, Kim-Marie; Ponich, Ashley A.; Hall, Dennis G. [Journal of the American Chemical Society, 2021]
[24]Chen, Liang; Gao, Meng; Lu, Cuifen; Ma, Chao; Ruan, Mengyao; Wen, Ziyang; Yang, Fan; Yang, Guichun [Chemical Communications, 2022, vol. 58, # 13, p. 2168 - 2171]

2
[ 40140-16-7 ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
98%	Stage #1: ethyl (p-methoxyphenyl)oxoacetate With sodium iodide In dichloromethane at 20℃; for 0.0833333h; Inert atmosphere; Stage #2: With chloro-trimethyl-silane In dichloromethane at 20℃; for 2h; Inert atmosphere; regioselective reaction;
	With sulfuric acid; palladium; acetic acid Hydrogenation_.weiteres Reagens: Bromwasserstoff;
	With palladium; acetic acid; zinc(II) chloride Hydrogenation_.weiteres Reagens: Chlorwasserstoff;

	Multi-step reaction with 2 steps 1.1: boron trifluoride diethyl etherate / dichloromethane / 20 °C / Inert atmosphere 2.1: sodium iodide; chloro-trimethyl-silane / dichloromethane / 15 h / 20 °C / Inert atmosphere; Green chemistry 2.2: 20 °C / Inert atmosphere; Green chemistry
	Multi-step reaction with 2 steps 1.1: boron trifluoride diethyl etherate / dichloromethane / 20 °C / Inert atmosphere 2.1: sodium iodide; chloro-trimethyl-silane / dichloromethane / 24 h / 20 °C / Inert atmosphere; Green chemistry 2.2: 20 °C / Inert atmosphere; Green chemistry
	Multi-step reaction with 2 steps 1.1: boron trifluoride diethyl etherate / dichloromethane / 20 °C / Inert atmosphere 2.1: sodium iodide; chloro-trimethyl-silane / dichloromethane / 24 h / 20 °C / Inert atmosphere; Green chemistry 2.2: 20 °C / Inert atmosphere; Green chemistry

Reference： [1]Yuan, Ling-Zhi; Zhao, Guangkuan; Hamze, Abdallah; Alami, Mouad; Provot, Olivier [Advanced Synthesis and Catalysis, 2017, vol. 359, # 15, p. 2682 - 2691]
[2]Kindler; Metzendorf; Kwok [Chemische Berichte, 1943, vol. 76, p. 308,314]
[3]Kindler; Metzendorf; Kwok [Chemische Berichte, 1943, vol. 76, p. 308,314]
[4]Zhao, Guangkuan; Yuan, Ling-Zhi; Alami, Mouad; Provot, Olivier [Advanced Synthesis and Catalysis, 2018, vol. 360, # 13, p. 2522 - 2536]
[5]Zhao, Guangkuan; Yuan, Ling-Zhi; Alami, Mouad; Provot, Olivier [Advanced Synthesis and Catalysis, 2018, vol. 360, # 13, p. 2522 - 2536]
[6]Zhao, Guangkuan; Yuan, Ling-Zhi; Alami, Mouad; Provot, Olivier [Advanced Synthesis and Catalysis, 2018, vol. 360, # 13, p. 2522 - 2536]

3
[ 14062-18-1 ]
[ 104-01-8 ]

Yield	Reaction Conditions	Operation in experiment
92%	With sodium hydroxide In methanol for 4h; Ambient temperature;
91%	With water; sodium hydroxide In 1,4-dioxane at 60℃; for 2h;	11 Preparation of p-Methoxyphenylacetic Acid from p-Methoxy Toluene and Ethanol p-Methoxy toluene (1.83 g), ethanol (46 mg), di-tert-butyl peroxide (73 mg, 1 equivalent), and Pd(Xantphos)Cl2 (3.8 mg, 1 mol %) were added into a reaction kettle, into which 10 atm carbon monoxide was introduced. The reaction was heated to 120° C., and stirred at this constant temperature for 16 h. After the reaction was completed, carbon monoxide was discharged, and 82 mg ethyl p-methoxyphenylacetate was obtained by column chromatography, in a yield of 85%. 1HNMR (400 MHz, CDCl3) δ 1.23 (t, J=6.8 Hz, 3H), 3.54 (s, 2H), 3.79 (s, 3H), 4.11 (q, J=6.8 Hz, 2H), 6.84-6.88 (m, 2H), 7.18-7.22 (m, 2H); 13CNMR (100 MHz, CDCl3) δ 14.2, 40.5, 55.3, 60.8, 113.9, 126.3, 130.3, 158.7, 171.9; HRMS (ESI) calcd. for C11H14NaO3 [M+Na]: 217.0835. found: 217.0838. The ethyl p-methoxyphenylacetate obtained was dissolved in 1,4-dioxane. 6 N sodium hydroxide solution was added, and the reaction was heated to 60° C. After 2 h of reaction, the pH value was adjusted to 1 by adding 2 N hydrochloric acid. After removing the organic solvent under reduced pressure, 64 mg product p-methoxyphenylacetic acid was obtained by extraction with ethyl acetate, and the yield of hydrolysis was 91%.
67%	Stage #1: ethyl p-methoxyphenylacetate With water; sodium hydroxide In methanol at 20℃; for 1h; Stage #2: With hydrogenchloride In water	To a solution of ethyl 2-(4-methoxyphenyl) acetate (12 g, 0.06 mol) in MeOH (150 mL) was added dropwise a solution of NaOH (9.8 g, 0.24 mol) in water (50 mL). The mixture was then stirred at RT for 1 h and concentrated in vacuo, the residue was acidified with HCl (IN) and extracted with EtOAc (2 x 400 mL). The combined organic layers were washed with water, dried over Na2SO4 and concentrated in vacuo to afford 2-(4- methoxyphenyl) acetic acid (10 g, 67 %) as a yellow oil.

With potassium hydroxide

Reference： [1]Giordano, Claudio; Castaldi, Graziano; Casagrande, Francesco; Belli, Aldo [Journal of the Chemical Society. Perkin transactions I, 1982, # 11, p. 2575 - 2582]
[2]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES - US2013/303798, 2013, A1 Location in patent: Paragraph 0018; 0048; 0049
[3]Current Patent Assignee: FORUM PHARMACEUTICALS INC - WO2009/158393, 2009, A1 Location in patent: Page/Page column 61
[4]Kindler; Metzendorf; Kwok [Chemische Berichte, 1943, vol. 76, p. 308,314]

4
[ 14062-18-1 ]
[ 702-23-8 ]

Yield	Reaction Conditions	Operation in experiment
99%	With C30H34Cl2N2P2Ru; potassium methanolate; hydrogen; In tetrahydrofuran; at 100℃; under 38002.6 - 76005.1 Torr; for 5h;Glovebox; Autoclave;	General procedure: In a glove box, add a ruthenium complex Ia (0.3 to 0.7 mg, 0.0002 to 0.001 mmol) to a 300 mL autoclave,Potassium methoxide (35-700 mg, 0.5-10 mmol), tetrahydrofuran (4-60 mL), and ester compounds (10-200 mmol).After sealing the autoclave, take it out of the glove box and fill it with 50 100atm of hydrogen.The reaction kettle was heated and stirred in an oil bath at 100 C for 10 to 336 hours.After the reaction kettle was cooled in an ice-water bath for 1.5 hours, the excess hydrogen was slowly released.The solvent was removed from the reaction solution under reduced pressure, and the residue was purified with a short silica gel column to obtain an alcohol compound. The results are shown in Table 5.

Reference： [1]Patent: CN110357923,2019,A .Location in patent: Paragraph 0301-0303; 0305
[2]Organic Letters,2020,vol. 22,p. 3642 - 3648
[3]Synthesis,2004,p. 1003 - 1006
[4]Journal of the Chemical Society,1959,p. 3714,3718
[5]Canadian Journal of Chemistry,1974,vol. 52,p. 749 - 760
[6]Journal of Organic Chemistry,1970,vol. 35,p. 2568 - 2571
[7]Chemistry - A European Journal,2011,vol. 17,p. 7414 - 7417
[8]Patent: DE164294,

5
[ 34006-60-5 ]
[ 100-66-3 ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
	With acetic acid Hydrieren der Reaktionsloesung an Palladium;

Reference： [1]Quelet; Gavarret [Bulletin de la Societe Chimique de France, 1950, p. 1075,1078]

6
[ 4360-47-8 ]
[ 14062-18-1 ]
[ 132604-96-7 ]

Yield	Reaction Conditions	Operation in experiment
82%	With sodium amide In diethyl ether at 30℃; for 1h;

Reference： [1]Petit; Nallet; Guillard; Dreux; Chermat; Poncelet; Bulach; Simon [European Journal of Medicinal Chemistry, 1990, vol. 25, # 8, p. 641 - 652]

7
[ 104-92-7 ]
[ 681-94-7 ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
47%	With zinc dibromide In N,N-dimethyl-formamide at 80℃; for 5h;

Reference： [1]Kosugi, Masanori; Negishi, Yoshikazu; Kameyama, Masayuki; Migita, Toshihiko [Bulletin of the Chemical Society of Japan, 1985, vol. 58, # 11, p. 3383 - 3384]

8
[ 14062-18-1 ]
[ 77629-83-5 ]

Yield	Reaction Conditions	Operation in experiment
100%	With N-Bromosuccinimide; dibenzoyl peroxide In tetrachloromethane for 3h; Heating;
94%	With N-Bromosuccinimide In tetrachloromethane; water for 5h; Heating / reflux;	1.1D.4B To a solution of the product of Preparation 4A (40 g, 200 mmol) in carbon tetrachloride (500 mL) was added N-bromosuccinimide (37 g, 206 mmol) and hydrobromic acid (4 drops of 48% aqueous solution). The resulting mixture was heated to reflux and maintained at that temperature for 5 hours then cooled to room temperature, filtered, and concentrated. The resulting oil was purified by flash chromatography (silica gel, chloroform) to give 51.1 g (94%) of the above-identified product as a colorless oil: 1H-NMR (d, DMSO) 1.19 (t, J=8.4 Hz, 3H), 3.77 (s, 3H), 4.18 (m, 2H), 5.88 (s, 1H), 6.95 (d, J=8.4 Hz, 2H), 7.50 (d, J=8.4 Hz, 2H); MS (FD) 272, 274 (M+); Anal. Calc'd for C11H13BrO3: C, 48.37; H, 4.80. Found: C, 48.52, 4.77.
91%	With N-Bromosuccinimide In tetrachloromethane; water for 5h; Heating / reflux;	1.a To a solution of a compound of the formula (40 g, 200 mmol) in carbon tetrachloride (500 mL) is added N-bromosuccinimide (37 g, 206 mmol) and 4 drops of 48% HBr. The reaction mixture is refluxed for 5 h, filtered and concentrated to dryness. The resulting oil is flash chromatographed on silica gel using chloroform as eluant to afford 49.5 g (91%) of the bromide as a colorless oil. This material is immediately dissolved in DMF (500 mL) and to this is added 4-nitroimidazole (20.5 g, 181 mmol) and potassium carbonate (75 g, 543 mmol). The reaction mixture is stirred overnight at ambient temperature, filtered and concentrated to dryness. The resulting oil is partitioned between ethyl acetate and water and extracted with ethyl acetate. The combined organics are washed with brine, dried over sodium sulfate, filtered and concentrated to dryness. The resulting oil is absorbed onto a silica pad and flash chromatographed on silica gel using 30-70% ethyl acetates/hexanes to yield 8 (33.6 g, 61%) as an orange oil that solidifies upon sitting. 1H-NMR (300 MHz, DMSO): 1.17 (t, J=7.2 Hz, 3H), 3.78 (s, 3H), 4.25 (q, J=7.2 Hz, 2H), 6.57 (s, 1H), 7.02 2H), 7.46 (d, J=8.7 Hz, 2H), 7.92 (s, 1H), 8.38 (s, 1H); Anal. Calc'd for C14H15B3O5: C, 55.08; H, 4.95; N, 13.76. Found: C, 54.93; H, 4.89; N, 13.82; MS m/z 306 (M+).

90%	With N-Bromosuccinimide; hydrogen bromide In tetrachloromethane Heating;
78%	With N-Bromosuccinimide In tetrachloromethane for 25h; Heating;
68%	With N-Bromosuccinimide; dibenzoyl peroxide In tetrachloromethane Reflux;
	With N-Bromosuccinimide; Perbenzoic acid In tetrachloromethane Heating; Yield given;
	With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile)
	With N-Bromosuccinimide
	With N-Bromosuccinimide In chloroform for 24h; Heating / reflux;	7 2. Synthesis of carboxylic acid intermediates; General procedure for synthesis of compounds 10 to 16; The appropriate phenyl acetic acid 10 was dissolved in anhydrous ethanol and refluxed in the presence of a catalytic amount of sulfuric acid to produce the ethyl ester 11. The ethyl ester was then refluxed in chloroform for 24 h using an equimolar amount of freshly recrystallised λ/-bromosuccinimide and a catalytic quantity of benzoyl peroxide to produce the α-bromo-arylester 12. The pyrrole 14 was produced by refluxing of the appropriate aminophenol (or may be prepared from an aminopyridinol) 13 in glacial acetic acid for 4 h using a molar equivalent of 2,5-dimethyoxytetrahydrofuran (mixture of cis- and trans- isomers). The pyrrole 14 was then deprotonated at the hydroxyl position by use of sodium hydride in dry tetrahydrofuran (THF) at 0 0C for 1 h followed by coupling an equimolar quantity of the ς-bromo-arylester 12 in dry THF overnight to produce the ethylester-acetamide 15. Hydrolysis of the ethyl ester 15 to the corresponding acid 16 was achieved using a 10% sodium hydroxide solution in ethanol/THF (1 :1 ), stirring at room temperature for 2 h.(4-Methoxy-phenyl)-(2-pyrrol-1-yl-pyridin-3-yloxy)-acetic acid (16a); MS-ESI: m/z 325.1 (99%, M+1 ). 1H-NMR (CD3OD) δ 3.84 (3H, s), 5.89 (1H, s), 6.31 (2H, t, J=2A Hz), 6.96 (2H, d, J=9 Hz), 7.22 (1 H, q), 7.50 (2H, d, J=9 Hz), 7.57 (1 H, d), 7.74 (2H, t, J=2.4 Hz), 8.06 (1 H, dd).
	With N-Bromosuccinimide; dibenzoyl peroxide In tetrachloromethane for 3h; Reflux;
	With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In tetrachloromethane for 5h; Reflux;
	With N-Bromosuccinimide; dibenzoyl peroxide In tetrachloromethane Reflux;
	With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In tetrachloromethane for 6h; Inert atmosphere; Reflux;

Reference： [1]Sharma, Vasudha; Tepe, Jetze J. [Organic Letters, 2005, vol. 7, # 22, p. 5091 - 5094]
[2]Current Patent Assignee: ELI LILLY & CO - US6828331, 2004, B1 Location in patent: Page column 29
[3]Current Patent Assignee: ELI LILLY & CO - US2005/277677, 2005, A1 Location in patent: Page/Page column 5
[4]Epstein, Joseph W.; Brabander, Herbert J.; Fanshawe, William J.; Hofmann, Corris M.; McKenzie, Thomas C.; et al. [Journal of Medicinal Chemistry, 1981, vol. 24, # 5, p. 481 - 490]
[5]Nacci; Fiorini; Garofalo; Cagnotto [Il Farmaco, 1990, vol. 45, # 5, p. 545 - 557]
[6]Chiba, Shunsuke; Zhang, Line; Ang, Gim Yean; Hui, Benjamin Wei-Qiang [Organic Letters, 2010, vol. 12, # 9, p. 2052 - 2055]
[7]Wasserman; Hlasta; Tremper; Wu [Journal of Organic Chemistry, 1981, vol. 46, # 15, p. 2999 - 3011]
[8]Lugar, Charles W.; Clay, Michael P.; Lindstrom, Terry D.; Woodson, Andrea L.; Smiley, David; Heiman, Mark L.; Dodge, Jeffrey A. [Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 23, p. 5873 - 5876]
[9]Bencivenni, Giorgio; Lanza, Tommaso; Leardini, Rino; Minozzi, Matteo; Nanni, Daniele; Spagnolo, Piero; Zanardi, Giuseppe [Journal of Organic Chemistry, 2008, vol. 73, # 12, p. 4721 - 4724]
[10]Current Patent Assignee: UNIVERSITY OF SYDNEY - WO2009/79683, 2009, A1 Location in patent: Page/Page column 44-46
[11]Zhou, Xiaorong; Fan, Zili; Zhang, Zhiyin; Lu, Ping; Wang, Yanguang [Organic Letters, 2016, vol. 18, # 18, p. 4706 - 4709]
[12]Frota, Carlise; Polo, Ellen Christine; Esteves, Henrique; Correia, Carlos Roque Duarte [Journal of Organic Chemistry, 2018, vol. 83, # 4, p. 2198 - 2209]
[13]Ishizuki, Kuniaki; Oka, Hironori; Aoki, Daisuke; Goseki, Raita; Otsuka, Hideyuki [Chemistry - A European Journal, 2018, vol. 24, # 13, p. 3170 - 3173]
[14]Tang, Shi; Yang, Sheng-Wen; Sun, Hongwei; Zhou, Yali; Li, Juan; Zhu, Qiang [Organic Letters, 2018, vol. 20, # 7, p. 1832 - 1836]

9
[ 14062-18-1 ]
[ 24021-11-2 ]

Yield	Reaction Conditions	Operation in experiment
70%	With hydrogen fluoride; triethylamine electrochemical fluorination;
61%	With triethylamine tris(hydrogen fluoride) In dichloromethane at 0℃; for 3h; Electrochemical reaction;

Reference： [1]Laurent, E.; Marquet, B.; Tardivel, R.; Thiebault, H. [Journal of Fluorine Chemistry, 1985, vol. 29, p. 193]
[2]Dinoiu, Vasile; Fukuhara, Tsuyoshi; Miura, Kaori; Yoneda, Norihiko [Journal of Fluorine Chemistry, 2003, vol. 121, # 2, p. 227 - 231]

10
[ 64-17-5 ]
[ 201230-82-2 ]
[ 6258-60-2 ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
68%	With dicobalt octacarbonyl; water at 190℃; for 24h;

Reference： [1]Shim, Sang Chul; Antebi, Shlomo; Alper, Howard [Journal of Organic Chemistry, 1985, vol. 50, # 1, p. 147 - 149]

11
[ 14062-18-1 ]
[ 95-92-1 ]
[ 104886-15-9 ]

Yield	Reaction Conditions	Operation in experiment
89%	With sodium methylate
85%	With ethanol; sodium In ethanol for 48h; Ambient temperature;
58%	With sodium ethanolate In ethanol for 0.5h;

Reference： [1]Jefford, Charles W.; Zaslona, Alexander [Tetrahedron Letters, 1985, vol. 26, # 49, p. 6035 - 6038]
[2]Jefford, Charles W.; Kubota, Tadatoshi; Zaslona, Alexander [Helvetica Chimica Acta, 1986, vol. 69, p. 2048 - 2061]
[3]Tyman, John H. P.; Payne [Journal of Chemical Research, 2006, # 11, p. 691 - 695]

12
[ 14062-18-1 ]
[ 109-94-4 ]
ethyl 2-(4-methoxyphenyl)-2-formyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With ethanol; sodium In diethyl ether 1.) 0 deg C, 2 h, 2.) room temp., 14 h;
	With sodium hydride
	With sodium hydride at 20℃;

	With sodium hydride In diethyl ether; mineral oil at 40℃; for 4h; Inert atmosphere;	6.2.1 Ethyl 2-formyl-2-aryl acetate (5a-g) General procedure: To a suspension of sodium hydride (49.4mmol, 60% dispersion in oil) in anhydrous diethyl ether (150mL) under a nitrogen atmosphere was added ethyl formate 4 (61.65mmol) dropwise, followed by the addition of ethyl 2-arylacetate 3 (41.1mmol) at room temperature. The reaction mixture was stirred at 40°C for 4h, quenched with water (100mL), and the ethereal layer was separated. The aqueous layer was washed with ether (100mL), acidified with 10% HCl (8mL), and extracted with ethyl acetate (3×150mL). The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure to give ethyl 2-formyl-2-aryl acetate 5 as colourless oil. The compound was used in subsequent reactions without further purification.
	With sodium In diethyl ether at 0 - 20℃;	2. General procedure for preparation of α-substituted-β-enamino esters 1a-1p^[1] General procedure: To a solution of ester 8 (20 mmol) in anhydrous ethyl ether was added ethyl formate (3.2 mL,40 mmol) at 0oC. Then sodium (0.92 g, 40 mmol) was added slowly. The reaction mixture wasstirred at room temperature. After completion of the reaction, the mixture was poured into icewater and extracted with Et2O (3×30 mL). The aqueous phase was acidified with a solution of 2NHCl to PH 3. Followed an extraction with Et2O (3×30 mL) and the organic layers were combined,dried over Na2SO4, filtered and concentrated in vacuum, leading to aldehyde 9 as a yellow oil which was used in the next step without further purification. Then 9 was dissolved in anhydrousdichloromethane and p-methoxyaniline (2.95 g, 24 mmol) was added, the reaction mixture wasstirred overnight at room temperature, the solvent was evaporated and the residue was subjected tochromatography to afford -enamino ester 1.

Reference： [1]Taber, Douglass F.; Mack, James F.; Rheingold, Arnold L.; Geib, Steven J. [Journal of Organic Chemistry, 1989, vol. 54, # 16, p. 3831 - 3836]
[2]Snyder, Lawrence B.; Meng, Zhaoxing; Mate, Robert; D'Andrea, Stanley V.; Marinier, Anne; Quesnelle, Claude A.; Gill, Patrice; Den Bleyker, Kenneth L.; Fung-Tomc, Joan C.; Frosco, MaryBeth; Martel, Alain; Barrett, John F.; Bronson, Joanne J. [Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 18, p. 4735 - 4739]
[3]Location in patent: scheme or table Masurier, Nicolas; Debiton, Eric; Jacquemet, Alicia; Bussière, Antoine; Chezal, Jean-Michel; Ollivier, Anthony; Tétégan, Daté; Andaloussi, Mounir; Galmier, Marie-Joseph; Lacroix, Jacques; Canitrot, Damien; Teulade, Jean-Claude; Gaudreault, René C.; Chavignon, Olivier; Moreau, Emmanuel [European Journal of Medicinal Chemistry, 2012, vol. 52, p. 137 - 150]
[4]Rajput, Santosh; Gardner, Christopher R.; Failes, Timothy W.; Arndt, Greg M.; Black, David Stc.; Kumar, Naresh [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 1, p. 105 - 115]
[5]Shu, Chang; Hu, Xiao-Yan; Li, Shuai-Shuai; Yuan, Wei-Cheng; Zhang, Xiao-Mei [Synlett, 2014, vol. 25, # 13, p. 1879 - 1882]

13
[ 14062-18-1 ]
[ 109-94-4 ]
[ 101987-52-4 ]

Yield	Reaction Conditions	Operation in experiment
95%	With sodium hydride at 20℃; for 5h;	4.1 In step (1), 10 mmol of ethyl 4-methoxyphenylacetate (10 mmol) was dissolved in 20 times the amount of 200 mmol of ethyl CHOOEt at room temperature. Under magnetic stirring, four times the amount of 40 mmol NaH, and then continue the reaction 5h, distilled off excess ethyl CHOOEt, carefully added 15g crushed ice, with 150mL CH2Cl2Divided three times, saturated brine, anhydrous MgSO4Dry, filter and evaporate methylene chloride CH2Cl2, 2.1 g of 2- (4-methoxyphenyl) -2-ethoxycarbonylvinyl alcohol was obtained as pale yellow liquid with a yield of 95%.
95%	With sodium hydride at 20℃; for 5h;	4.1 In step (1), 10 mmol of ethyl 4-methoxyphenylacetate was dissolved in 20-fold amount at room temperature.In 200 mmol ethyl formate CHOOEt, add 4 times 40 mmol of NaH in 4 batches with magnetic stirring. Add 5 minutes of reaction to continue the reaction. Remove excess ethyl formate CHOOEt. Carefully add 15 g of crushed ice and divide 3 times with 150 mL of CH2C12. The extract was washed with saturated brine, dried over anhydrous MgSCU, filtered, and dichloromethane CH2CI2 was evaporated to give a pale yellow liquid of 2-(4-methoxyphenyl)-2-ethoxycarbonylvinyl alcohol (2.1 g). 95%.
94%	With sodium hydride for 2.5h; Ambient temperature;

86%	Stage #1: ethyl p-methoxyphenylacetate With sodium hydride In mineral oil; benzene at 20℃; for 0.0833333h; Cooling with ice; Stage #2: formic acid ethyl ester In mineral oil; benzene at 20℃; for 3h; Cooling with ice; Stage #3: With hydrogenchloride; water In ethyl acetate; mineral oil; benzene Cooling with ice;	3 Ethyl α-(hydroxymethylene)-4-methoxyphenyl acetate Sodium hydride (60% in oil) (467 mg, 11.7 mmol) was added to a benzene solution (10 ml) of ethyl 4-methoxyphenyl acetate (2.0 g, 10.3 mmol), while being cooled with ice. The mixture was stirred at room temperature for 5 minutes. The stirred mixture was cooled with ice again; ethyl formate (1.02 ml, 12.6 mmol) was added thereto and stirred at room temperature for 3 hours. While being cooled with ice, water and ethyl acetate were added to the reaction mixture, and then 2N hydrochloric acid (6 ml) was added to separate the reaction mixture into two layers. The organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 4:1). The purified product was concentrated under reduced pressure to thereby obtain 1.97 g of slightly reddish-brown oily ethyl α-(hydroxymethylene)-4-methoxyphenyl acetate (yield: 86%). The resulting object was purged with nitrogen and stored in a freezer. 1H-NMR (CDCl3) δppm: 1.28 (3H, t, J = 7.1 Hz), 3.81 (3H, s), 4.28 (2H, q, J = 7.1 Hz) , 6.87 (2H, d, J = 8.8 Hz), 7-7.26 (3H, m), 12.02 (1H, d, J = 12.5 Hz).
86%	Stage #1: ethyl p-methoxyphenylacetate With sodium hydride In benzene at 20℃; for 0.0833333h; Cooling with ice; Stage #2: formic acid ethyl ester at 20℃; for 3h; Cooling with ice;	1 α- (hydroxymethylene) -4-methoxyphenylacetic acid ethyl ester To a solution of 2.0 g (10.3 mmol) of 4-methoxyphenylacetic acid ethyl ester in benzene (10 mL) was added, under ice cooling,467 mg (11.7 mmol) of sodium hydride (60% oily) was added,The mixture was stirred at room temperature for 5 minutes.The mixture after stirring was cooled again with ice,1.02 ml (12.6 mmol) of ethyl formate was added,And the mixture was stirred at room temperature for 3 hours.below freezing,Water and ethyl acetate were added to the reaction solution,2 N hydrochloric acid 6 mL was added,And separated.The organic layer was concentrated under reduced pressure,The residue was purified by silica gel column chromatography (n-hexane: ethyl acetate =4: 1).The purified product was concentrated under reduced pressure to obtain α- (hydroxymethylene) -4-methoxyphenylacetic acid ethyl ester (1.97 g, yield 86%) as a slightly reddish brown oil.
86%	Stage #1: ethyl p-methoxyphenylacetate With sodium hydride In benzene at 0 - 20℃; for 0.0833333h; Stage #2: formic acid ethyl ester In benzene at 0 - 20℃; for 3h;	46 Reference Example 46; Ethyl α- (hydroxymethylene)-4-methoxyphenyl acetate Sodium hydride (60% in oil) (467 mg, 11.7 mmol) was added to a benzene solution (10 ml) of ethyl 4-methoxyphenyl acetate (2.0 g, 10.3 mmol), while being cooled with ice. The mixture was stirred at room temperature for 5 minutes. The stirred mixture was cooled with ice again; ethyl formate (1.02 ml, 12.6 mmol) was added thereto, and stirred at room temperature for 3 hours. While being cooled with ice, water and ethyl acetate were added to the reaction mixture, and then 2N hydrochloric acid (6 ml) was added to separate the reaction mixture into two layers. The organic layer was concentrated under reduced pressure, and the residue was then purified by silica gel column chromatography (n-hexane : ethyl acetate = 4 : 1). The purified product was concentrated under reduced pressure to thereby obtain 1.97 g of oily slightly reddish-brown ethyl α- (hydroxymethylene) -4- methoxyphenyl acetate (yield: 86%) . The resultant compound undergoes nitrogen substitution, and was stored in a freezer. 1H-NMR (CDCl3) dppm:1.28 (3H, t, J=7.1 Hz), 3.81 (3H, s), 4.28 (2H, q, J=7.1 Hz), 6.87 (2H, d, J=8.8 Hz), 7.16-7.26 (3H, m) , 12.02 (IH, d, J=12.5 Hz)
	Stage #1: ethyl p-methoxyphenylacetate; formic acid ethyl ester With sodium hydride at 20℃; for 12h; Stage #2: With hydrogenchloride In water	2.4 Preparation 2.4; Ethyl 2-(4-methoxyphenyl)-3-hydroxy-2-propenoate (III); 8.9 ml of ethyl p-methoxyphenylacetate are dissolved in 80 ml of ethyl formate. 4.6 g of 50% NaH are added portionwise and then the mixture is stirred at ambient temperature for 12 hours. It is poured onto a 1N HCl solution and then extraction is carried out with AcOEt. Purification is carried out by chromatography on a silica column eluted with an AcOEt/heptane (05/95; v/v) mixture to produce 4.0 g of the expected compound in the liquid form. NMR CDCl3 (200 MHz): 1.30 ppm:t:3H; 3.83 ppm:s:3H; 4.29 ppm:q:2H; 6.89-7.21 ppm:unresolved peak:5H.
	With sodium hydride at 20℃; for 3h;	1.1 Example 1 (1) Ethyl 4-methoxybenzeneacetate is dissolved in ethyl formate CHOOEt at room temperature, and sodium hydride NaH is added in 4 batches under magnetic stirring.The ratio of the amount of the substance of ethyl 4-methoxybenzeneacetate, ethyl formate CHOOEt and sodium hydride NaH is 1:2:3, and the reaction is continued for 3 hours after the addition, and the excess ethyl formate CHOOEt is distilled off.Carefully add crushed ice 10 times the mass of ethyl 4-methoxyphenylacetate, extract with twice the volume of aqueous solution of CH2Cl2, extract three times in total, and wash with saturated brine.Anhydrous magnesium sulfate MgSO4 drying, filtration, dichloromethane dichloromethane CH2Cl2 evaporated to give a light yellow liquid 2-(4-methoxyphenyl)-2-ethoxycarbonyl vinyl alcohol

Reference： [1]Current Patent Assignee: GUANGZHOU UNIVERSITY - CN107417611, 2017, A Location in patent: Page/Page column 0054; 0056
[2]Current Patent Assignee: NANJING UNIVERSITY; GUANGZHOU UNIVERSITY - CN107459481, 2017, A Location in patent: Paragraph 0030; 0054
[3]Beccalli, Egle M.; Rosa, Concetta La; Marchesini, Alessandro [Journal of Organic Chemistry, 1984, vol. 49, # 22, p. 4287 - 4290]
[4]Current Patent Assignee: OTSUKA HOLDINGS CO LTD - EP2364706, 2011, A1 Location in patent: Page/Page column 14
[5]Current Patent Assignee: OTSUKA HOLDINGS CO LTD - JP2018/123072, 2018, A Location in patent: Paragraph 0117
[6]Current Patent Assignee: OTSUKA HOLDINGS CO LTD - WO2008/150029, 2008, A1 Location in patent: Page/Page column 50-51
[7]Current Patent Assignee: SANOFI - US2005/288318, 2005, A1 Location in patent: Page/Page column 9
[8]Current Patent Assignee: GUANGZHOU UNIVERSITY; NANJING UNIVERSITY - CN107522656, 2017, A Location in patent: Paragraph 0028; 0029; 0037; 0045; 0052

14
[ 14062-18-1 ]
[ 7472-70-0 ]
1,4-bis(4-tolyl)-3,6-bis(4-methoxyphenyl)pyrrolo[3,2-b]pyrrol-2,5-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With sodium hexamethyldisilazane In tetrahydrofuran at -78 - 20℃; for 2h;

Reference： [1]Langer; Wuckelt; Doering [Journal of Organic Chemistry, 2000, vol. 65, # 3, p. 729 - 734]

15
[ 14062-18-1 ]
[ 40140-16-7 ]

Yield	Reaction Conditions	Operation in experiment
90%	With 2,6-dimethylpyridine; N-hydroxyphthalimide; tetrabutylammonium perchlorate; oxygen In water; acetonitrile at 60℃; Electrochemical reaction;	2.2. Procedures for synthesis of products 3 a-n General procedure: A 20 mL two-necked round-bottomed flask was charged with the substrate (0.50 mmol), NHPI (0.20 mmol), 2,6-lutidine (0.30 mmol) and n-Bu 4 NClO 4 (1.0 mmol). The flask was then equipped with a condenser, a carbon paper (1.0 cm ×1.0 cm) an- ode and a platinum net (1.0 cm ×1.0 cm) cathode, and flushed with oxygen. Acetonitrile (9.5 mL) and water (0.5 mL) were then added. The electrolysis was carried out at 60 °C using a constant current of 5 mA until cell voltage at 3.0 V. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was chromatographed through silica gel elut- ing with ethyl acetate/petroleum ether (4:1) to give the desired product.
99 % Chromat.	With N-hydroxyphthalimide; oxygen; cobalt(II) acetate In acetic acid at 40℃; for 24h;
	Multi-step reaction with 2 steps 1: 97 percent / 48 h / 60 °C 2: 95 percent / O₂, bisacenaphthalenethiophene (BANT) / CH₂Cl₂ / 0.5 h / -78 °C / Irradiation

	With ketoreductase-P₁-B₀₂; oxygen; NADPH; 9‑mesityl-10-methylacridinium perchlorate In water; acetonitrile at 23℃; for 24h; Irradiation; Enzymatic reaction;
	Multi-step reaction with 2 steps 1: 4-acetamidobenzenesulfonyl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile / 12 h / 20 °C / Inert atmosphere 2: oxygen; copper nanoparticles on activated carbon / 1,2-dichloro-ethane / 36 h / 30 °C / Schlenk technique
	Multi-step reaction with 2 steps 1: 4-acetamidobenzenesulfonyl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile / 0 - 23 °C / Inert atmosphere 2: acetic acid; tetra-(n-butyl)ammonium iodide / acetonitrile / 12 h / 20 °C / Electrochemical reaction; Green chemistry

Reference： [1]Xu, Leitao; Yi, Yangjie; Hu, Sideng; Ye, Jiao; Hu, Aixi [Electrochimica Acta, 2022, vol. 403]
[2]Wentzel, Bastienne B; Donners, Maurice P.J; Alsters, Paul L; Feiters, Martinus C; Nolte, Roeland J.M [Tetrahedron, 2000, vol. 56, # 39, p. 7797 - 7803]
[3]Wasserman, Harry H.; Ives, Jeffrey L. [Journal of Organic Chemistry, 1985, vol. 50, # 19, p. 3573 - 3580]
[4]Betori, Rick C.; May, Catherine M.; Scheidt, Karl A. [Angewandte Chemie - International Edition, 2019, vol. 58, # 46, p. 16490 - 16494][Angew. Chem., 2019, vol. 131, p. 16642 - 16646,5]
[5]Chu, Changhu; Dong, Wenwen; Lin, Jia; Teng, Jiangge; Wang, Zhiwei; Zhao, Rong [Organic and Biomolecular Chemistry, 2021, vol. 19, # 27, p. 6120 - 6126]
[6]Chen, Liang; Gao, Meng; Lu, Cuifen; Ma, Chao; Ruan, Mengyao; Wen, Ziyang; Yang, Fan; Yang, Guichun [Chemical Communications, 2022, vol. 58, # 13, p. 2168 - 2171]

16
[ 5720-07-0 ]
[ 105-36-2 ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
97%	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; N,N-diisopropyl-1,1-diphenylphosphanamine; water; potassium carbonate In tetrahydrofuran at 65℃; for 8h; Inert atmosphere;
84%	With potassium phosphate; tri-1-napthylphosphine In tetrahydrofuran at 20℃; for 16h;
77%	With potassium fluoride; benzyltriethylammonium bromide; tris-(o-tolyl)phosphine; bis(dibenzylideneacetone)-palladium⁽⁰⁾ In tetrahydrofuran at 60℃; for 24h; Inert atmosphere;

62%

With potassium carbonate at 80℃;

Reference： [1]Location in patent: experimental part Peng, Zhi-Yong; Wang, Jian-Ping; Cheng, Jiang; Xie, Xiao-Min; Zhang, Zhaoguo [Tetrahedron, 2010, vol. 66, # 42, p. 8238 - 8241]
[2]Goossen [Chemical Communications, 2001, # 7, p. 669 - 670]
[3]Location in patent: experimental part Zimmermann, Bettina; Dzik, Wojciech I.; Himmler, Thomas; Goossen, Lukas J. [Journal of Organic Chemistry, 2011, vol. 76, # 19, p. 8107 - 8112]
[4]Liu, Xing-Xin; Deng, Min-Zhi [Chemical Communications, 2002, # 6, p. 622 - 623]

17
[ 105-36-2 ]
[ 171364-79-7 ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
76%	With potassium phosphate; tri-1-napthylphosphine In tetrahydrofuran at 20℃;

Reference： [1]Goossen [Chemical Communications, 2001, # 7, p. 669 - 670]

18
[ 696-62-8 ]
[ 105-53-3 ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
70%	With tri-tert-butyl phosphine; caesium carbonate In 1,2-dimethoxyethane at 120℃; for 74h;

Reference： [1]Kondo; Inamoto; Uchiyama; Sakamoto [Chemical Communications, 2001, # 24, p. 2704 - 2705]

19
[ 14062-18-1 ]
[ 623-49-4 ]
[ 23197-67-3 ]

Yield	Reaction Conditions	Operation in experiment
81%	Stage #1: ethyl p-methoxyphenylacetate With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 1h; Stage #2: ethyl cyanoformate In tetrahydrofuran at 20℃; for 14h; Further stages.;
59%	Stage #1: ethyl p-methoxyphenylacetate With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1h; Stage #2: ethyl cyanoformate In tetrahydrofuran at -78 - 20℃;
	Stage #1: ethyl p-methoxyphenylacetate With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; Stage #2: ethyl cyanoformate In tetrahydrofuran at 20℃;

	Stage #1: ethyl p-methoxyphenylacetate With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 1h; Stage #2: ethyl cyanoformate In tetrahydrofuran at -78℃; for 2.5h; Stage #3: With water; ammonium chloride In tetrahydrofuran at 20℃; for 0.5h;	2.c.1 A solution of 1.0 M LiHMDS in THF (43.2 mL, 43.2 mmol) is added to a cold (-78°C) solution of 2c1 (Aldrich; 7.00 g, 36.0 mmol) in THF (300 mL). The reaction mixture is stirred at this temperature for 1 h. Ethyl cyanoformate (5.34 mL, 43.2 mmol) is added and the reaction mixture is stirred at -78°C for 30 min then allowed to warm to RT and maintained at this temperature for 3 h. Aqueous NH4CI solution is added and the mixture stirred at RT for 30 min. The mixture then is concentrated under reduced pressure, EtOAc is added and the phases are separated. The organic layer is washed with water and brine, dried (MgS04), filtered and concentrated under reduced pressure. The residue is purified by flash chromatography (DCM) to give compound 2c2.
	Stage #1: ethyl p-methoxyphenylacetate With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: ethyl cyanoformate In tetrahydrofuran at -78 - 20℃; Inert atmosphere;

Reference： [1]Bustos, Eduardo; Gotor-Fernandez, Vicente; Montejo-Bernardo, Jose; Garcia-Granda, Santiago; Gotor, Vicente [Organic Letters, 2007, vol. 9, # 21, p. 4203 - 4206]
[2]Katz, Christopher E.; Aube, Jeffrey [Journal of the American Chemical Society, 2003, vol. 125, # 46, p. 13948 - 13949]
[3]Rios-Lombardia, Nicolas; Busto, Eduardo; Garcia-Urdiales, Eduardo; Gotor-Fernandez, Vicente; Gotor, Vicente [Journal of Organic Chemistry, 2009, vol. 74, # 6, p. 2571 - 2574]
[4]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - WO2011/100838, 2011, A1 Location in patent: Page/Page column 31; 32
[5]Huang, Zhongxing; Low, Kam-Hung; Zhang, Suihan; Zheng, Yin; Zi, Weiwei [Journal of the American Chemical Society, 2022, vol. 144, # 4, p. 1951 - 1961]

20
[ 104-92-7 ]
[ 141-97-9 ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
40%	With potassium phosphate; tri tert-butylphosphoniumtetrafluoroborate In toluene at 90℃; for 16h;

Reference： [1]Zeevaart, Jacob G.; Parkinson, Christopher J.; De Koning, Charles B. [Tetrahedron Letters, 2004, vol. 45, # 22, p. 4261 - 4264]

21
[ 623-12-1 ]
[ 141-97-9 ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
75%	With potassium phosphate; di-tert-butyl (2'-methyl-[1,1'-biphenyl]-2-yl)phosphine In toluene at 90℃; for 16h;

Reference： [1]Zeevaart, Jacob G.; Parkinson, Christopher J.; De Koning, Charles B. [Tetrahedron Letters, 2004, vol. 45, # 22, p. 4261 - 4264]

22
[ 623-12-1 ]
[ 105-53-3 ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
87%	With palladium diacetate; 1,3-bis(alkyl)imidazolium chloride (LHX₄); caesium carbonate In 1,4-dioxane at 80℃; for 24h;

Reference： [1]Özdemir, Ismail; Yigit, Murat; Çetinkaya, Engin; Çetinkaya, Bekir [Tetrahedron Letters, 2004, vol. 45, # 30, p. 5823 - 5825]

23
[ 14062-18-1 ]
2-fluoro-6-trifluoromethylaniline [ No CAS ]
4,8-difluoro-3-(4-methoxyphenyl)quinolin-2(1H)-one [ No CAS ]
N-(2-fluoro-6-trifluoromethyl-phenyl)-2-(4-methoxy-phenyl)-acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 57% 2: 19%	With n-butyllithium; diisopropylamine In tetrahydrofuran at -78 - 20℃; for 8h;

Reference： [1]Kiselyov, Alexander S.; Piatnitski, Evgueni L.; Doody, Jacqueline [Organic Letters, 2004, vol. 6, # 22, p. 4061 - 4063]

24
[ 14062-18-1 ]
3-bromo-2-(trifluoromethyl)aniline [ No CAS ]
5-bromo-4-fluoro-3-(4-methoxyphenyl)quinolin-2(1H)-one [ No CAS ]
N-(3-bromo-2-trifluoromethyl-phenyl)-2-(4-methoxy-phenyl)-acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 63% 2: 12%	With n-butyllithium; diisopropylamine In tetrahydrofuran at -78 - 20℃; for 8h;

Reference： [1]Kiselyov, Alexander S.; Piatnitski, Evgueni L.; Doody, Jacqueline [Organic Letters, 2004, vol. 6, # 22, p. 4061 - 4063]

25
[ 14062-18-1 ]
[ 88-17-5 ]
4-fluoro-3-(4-methoxyphenyl)quinolin-2(1H)-one [ No CAS ]
2-(4-methoxy-phenyl)-N-(2-trifluoromethyl-phenyl)-acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 71% 2: 8%	With n-butyllithium; diisopropylamine In tetrahydrofuran at -78 - 20℃; for 8h;

Reference： [1]Kiselyov, Alexander S.; Piatnitski, Evgueni L.; Doody, Jacqueline [Organic Letters, 2004, vol. 6, # 22, p. 4061 - 4063]

26
[ 1516-58-1 ]
[ 14062-18-1 ]
[ 849690-58-0 ]

Yield	Reaction Conditions	Operation in experiment
56%	Stage #1: ethyl p-methoxyphenylacetate With sodium ethanolate In ethanol at -10℃; Stage #2: o-azidonitrobenzene In ethanol at -10 - 20℃;

Reference： [1]Primofiore, Giampaolo; Da Settimo, Federico; Taliani, Sabrina; Salerno, Silvia; Novellino, Ettore; Greco, Giovanni; Cosimelli, Barbara; Besnard, François; Costa, Barbara; Montali, Marina; Martini, Claudia [Journal of Medicinal Chemistry, 2005, vol. 48, # 8, p. 2936 - 2943]

27
[ 14062-18-1 ]
[ 104503-85-7 ]
[ 849690-65-9 ]

Yield	Reaction Conditions	Operation in experiment
46%	Stage #1: ethyl p-methoxyphenylacetate With sodium ethanolate In ethanol at -10℃; Stage #2: 2-azido-4-chloro-1-nitrobenzene In ethanol at -10 - 20℃;

Reference： [1]Primofiore, Giampaolo; Da Settimo, Federico; Taliani, Sabrina; Salerno, Silvia; Novellino, Ettore; Greco, Giovanni; Cosimelli, Barbara; Besnard, François; Costa, Barbara; Montali, Marina; Martini, Claudia [Journal of Medicinal Chemistry, 2005, vol. 48, # 8, p. 2936 - 2943]

28
[ 14062-18-1 ]
[ 185040-32-8 ]
6-(4-methoxyphenyl)-8-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one [ No CAS ]

Reference： [1]Tetrahedron Letters,2006,vol. 47,p. 3177 - 3180

29
[ 14062-18-1 ]
[ 105-58-8 ]
[ 23197-67-3 ]

Yield	Reaction Conditions	Operation in experiment
75%	With sodium hydride In tetrahydrofuran; hexane at 60℃;
69%	With sodium hydride In tetrahydrofuran; mineral oil for 87h; Reflux;
60%	With sodium hydride In tetrahydrofuran Inert atmosphere; Reflux;

	In hydrogenchloride; (2S)-N-methyl-1-phenylpropan-2-amine hydrate; N,N-dimethyl-formamide; toluene	R.26.a Ethyl 2-[4-[((3S)-1-tert-butoxycarbonyl-3-pyrrolidinyl)oxy]phenyl]-2-ethoxycarbonylacetate a) 27.7 g of ethyl 4-methoxyphenylacetate and 34 ml of diethyl carbonate were dissolved in 150 ml of N,N-dimethylformamide, and the solution was subjected to reflux under heating, while gradually adding 6.5 g of sodium hydride for 1 hour. After further refluxing under heating for 2 hours, the resulting reaction solution was poured into a mixture of ice water and hydrochloric acid, followed by extraction with ethyl acetate. The resulting organic layer was washed with water, and then dried to distill off the solvent. The residue thus obtained was purified by silica gel column chromatography using toluene as an eluant, thereby obtaining 26.7 g of ethyl 2-ethoxycarbonyl-2-(4-methoxyphenyl)acetate in the form of light yellow oil. 1 H-NMR (CDCl3) δ: 1.25 (6H, t, J=7.0Hz), 3.79 (3H, s), 4.20 (4H, q, J=7.0Hz), 4.55 (1H, s), 6.88 (2H, d, J=8.0Hz), 7.32 (2H, d, J=8.0Hz)
	With sodium In ethanol	A Ingredients: Part A Diethyl 4-methoxyphenylmalonate Ingredients: 150 ml of absolute ethanol 7.5 g (0.33 mol) of sodium 300 ml of diethylcarbonate 62.5 g (0.3 mol) of ethyl 4-methoxyphenylacetate
34.2 g	With sodium for 3h; Heating / reflux;
	With sodium hydride In tetrahydrofuran at 0℃; for 4h; Reflux;
	Stage #1: ethyl p-methoxyphenylacetate With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; Stage #2: Diethyl carbonate In tetrahydrofuran at -78 - 20℃; for 14.5h; Inert atmosphere;

Reference： [1]Matulenko, Mark A.; Paight, Ernest S.; Frey, Robin R.; Gomtsyan, Arthur; DiDomenico Jr., Stanley; Jiang, Meiqun; Lee, Chih-Hung; Stewart, Andrew O.; Yu, Haixia; Kohlhaas, Kathy L.; Alexander, Karen M.; McGaraughty, Steve; Mikusa, Joseph; Marsh, Kennan C.; Muchmore, Steven W.; Jakob, Clarissa L.; Kowaluk, Elizabeth A.; Jarvis, Michael F.; Bhagwat, Shripad S. [Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 4, p. 1586 - 1605]
[2]Enoua, Guy Crepin; Uray, Georg; Stadlbauer, Wolfgang [Journal of Heterocyclic Chemistry, 2012, vol. 49, # 6, p. 1415 - 1421]
[3]Bailey, William F.; Lambert, Kyle M.; Stempel, Zachary D.; Wiberg, Kenneth B.; Mercado, Brandon Q. [Journal of Organic Chemistry, 2016, vol. 81, # 24, p. 12116 - 12127]
[4]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - US5576343, 1996, A
[5]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US5643919, 1997, A
[6]Current Patent Assignee: ROCHE HOLDING AG - US6335332, 2002, B1 Location in patent: Page column 10
[7]Guo, Jia; Xu, Cong; Liu, Xiaowei; Wang, Mang [Organic and Biomolecular Chemistry, 2019, vol. 17, # 8, p. 2162 - 2168]
[8]Estrada, Carl D.; Ang, Hwee Ting; Vetter, Kim-Marie; Ponich, Ashley A.; Hall, Dennis G. [Journal of the American Chemical Society, 2021]

30
[ 696-62-8 ]
[ 141-97-9 ]
[ 5219-08-9 ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
1: 93% 2: 7%	With potassium carbonate In dimethyl sulfoxide at 80℃; for 20h;
1: 45% 2: 29%	With potassium carbonate In tetrahydrofuran at 100℃; for 24h;

Reference： [1]Zeevaart, Jacob G.; Parkinson, Christopher J.; de Koning, Charles B. [Tetrahedron Letters, 2007, vol. 48, # 18, p. 3289 - 3293]
[2]Lu, Biao; Wang, Bao; Zhang, Yihua; Ma, Dawei [Journal of Organic Chemistry, 2007, vol. 72, # 14, p. 5337 - 5341]

31
[ 50-00-0 ]
[ 14062-18-1 ]
[ 39729-00-5 ]

Yield	Reaction Conditions	Operation in experiment
89%	With tetra(n-butyl)ammonium hydrogensulfate; potassium carbonate In toluene at 80℃; for 12h;
70%	With tetra-(n-butyl)ammonium iodide; potassium carbonate In toluene at 20 - 60℃; for 8h;
	With tetra-(n-butyl)ammonium iodide; potassium carbonate In toluene at 80 - 85℃; for 3.5h;

	With tetra-(n-butyl)ammonium iodide; potassium carbonate In toluene at 80℃; for 2h;	66 Intermediate 66a: 2- (4-METHOXY-PHENYL)-ACRYLIC acid ethyl ester A mixture of ethyl-4-methoxyphenethyl acetate (3.0 g, 15.44 MMOL), 95% PARAFOMALDEHYDE (732 mg, 23.16 MMOL), K2C03 (3.30 g, 23.88 MMOL), and BU4N 1 (171 mg, 0.463 MMOL) in toluene was heated at 80°C for two hours, cooled to room temperature, poured into water, and extracted with EtOAc for three times. The combined organic phase was dried over Na2SO4, concentrated in vacuo, and purified by flash column chromatography eluting with 10% EtOAc in hexanes to provide 2.14 G of intermediate 66a as a colorless OIL. H NMR (300 MHz, CD30D) 8 7.36 (d, 2H, J = 8. 67 HZ), 6.87 (d, 2H, J= 8.67 Hz), 6.64 (s, 1H), 5.81 (s, 1H), 4.28 (q, 2H, J = 7.16 Hz), 3.81 (s, 3H), 1.32 (t, 2H, J= 7.16 Hz). LCMS (ESI+) [M+H] /z Calc'd 207, found 207.
	With tetra-(n-butyl)ammonium iodide; potassium carbonate In toluene at 60℃;	General procedure: To a solution of ester (20 mmol, 1.0 equiv) in toluene (40 mL) was addedparaformaldehyde (1.80 g, 60 mmol, 3.0 equiv), K2CO3 (8.29 g, 60 mmol, 3.0 equiv),n-Bu4NI (370.0 mg, 1.0 mmol, 0.05 equiv). The reaction mixture was heated to 60 °Covernight. After the finish of reaction monitored by TLC, the reaction was cooled toroom temperature, water was added and the aqueous layer was extracted with Et2O(40 mL × 3). The combined organic layer was dried over anhydrous Na2SO4,concentrated in vacuo. The resulting residue was purified by column chromatographyto give the corresponding acrylate intermediate as a colorless oil. Then, a solution ofsubstituted amine (20 mmol, 2.0 equiv)in THF (13.0 mL) at 0°C was added a solutionof corresponding acrylate (10 mmol, 1.0 equiv) in THF (7.0 mL) via addition funnel.The reaction mixture was allowed to warm to ambient temperature then stirred atroom temperature for 24h, and concentrated under vacuum. The resulting residue waspurified by column chromatography to give the corresponding intermediate as a oil.Then to a solution of the oil in dichloromethane (20.0 mL) were added di-tert-butyldicarbonate (2.40 g, 11 mmol) and DMAP (122.0 mg, 1 mmol), and the mixture wasstirred at room temperature for 24h. Saturated aq. NH4Cl was added to the mixtureand the resulting mixture was extracted with dichloromethane. The combined organiclayer was washed with brine, dried over Na2SO4, filtered and evaporated in vacuo.The resulting residue was purified by column chromatography to give thecorresponding intermediate as a colorless oil. Then to a solution of the resulting oil inTHF/H2O (5 mL/5 mL) was added LiOH (1.20 g, 50 mmol, 5 equiv). The reactionmixture was heated at 60 °C overnight. After cooling to room temperature, thereaction was acidified using aqueous HCl (6 M), and the aqueous layer was extractedwith Et2O (20 mL × 3). The combined organic layer was washed with water and brine,dried over Na2SO4, and concentrated in vacuo to give the resulting product 4a-j as acolorless crystal, using for the next step without further purification.
	With tetra-(n-butyl)ammonium iodide; potassium carbonate In toluene at 60℃; for 8h;

Reference： [1]Chavan, Subhash P.; Pathak, Ashok B.; Pandey, Ankur; Kalkote, Uttam R. [Synthetic Communications, 2007, vol. 37, # 23, p. 4253 - 4263]
[2]Hu, Xu-Hong; Zhang, Jian; Yang, Xiao-Fei; Xu, Yun-He; Loh, Teck-Peng [Journal of the American Chemical Society, 2015, vol. 137, # 9, p. 3169 - 3172]
[3]Chavan, Subhash P.; Khobragade, Dushant A.; Thakkar, Mahesh; Kalkote, Uttam R. [Synthetic Communications, 2007, vol. 37, # 22, p. 3901 - 3906]
[4]Current Patent Assignee: PFIZER INC - WO2005/21554, 2005, A1 Location in patent: Page/Page column 78
[5]Yu, Meng; Zeng, Minghui; Pan, Zhaoping; Wu, Fengbo; Guo, Li; He, Gu [European Journal of Medicinal Chemistry, 2020, vol. 189]
[6]Jiang, Yuqin; Li, Pengfei; Li, Xingwei; Liu, Bingxian; Zhao, Jie [Organic Letters, 2020, vol. 22, # 19, p. 7475 - 7479]

32
[ 14062-18-1 ]
[ 77629-84-6 ]

Yield	Reaction Conditions	Operation in experiment
89%	With sodium azide; 4,4'-bis-(dichloroiodo)-biphenyl; triethylamine In 1,4-dioxane for 4h; Reflux;
	Multi-step reaction with 2 steps 1: 100 percent / N-bromosuccinimide; benzoyl peroxide / CCl₄ / 3 h / Heating 2: 82 percent / 15-crown-5; sodium azide / benzene / 8 h / 20 °C
	Multi-step reaction with 2 steps 1: NBS, benzoyl peroxide / CCl₄ / Heating 2: 94 percent / KN₃, 18-crown-6 / benzene / 6 h / Ambient temperature

	Multi-step reaction with 2 steps 1: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / tetrachloromethane / 6 h / Inert atmosphere; Reflux 2: sodium azide / acetonitrile / 20 °C
	Multi-step reaction with 2 steps 1: 4-toluenesulfonyl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile / 20 °C / Inert atmosphere; Schlenk technique 2: tris(pentafluorophenyl)borate; trimethylsilylazide / dichloromethane / 4 h / 0 - 20 °C / Inert atmosphere; Schlenk technique; Molecular sieve

Reference： [1]Location in patent: experimental part Telvekar, Vikas N.; Patile, Hemlata V. [Synthetic Communications, 2011, vol. 41, # 1, p. 131 - 135]
[2]Sharma, Vasudha; Tepe, Jetze J. [Organic Letters, 2005, vol. 7, # 22, p. 5091 - 5094]
[3]Wasserman; Hlasta; Tremper; Wu [Journal of Organic Chemistry, 1981, vol. 46, # 15, p. 2999 - 3011]
[4]Tang, Shi; Yang, Sheng-Wen; Sun, Hongwei; Zhou, Yali; Li, Juan; Zhu, Qiang [Organic Letters, 2018, vol. 20, # 7, p. 1832 - 1836]
[5]San, Htet Htet; Wang, Chun-Ying; Zeng, Hai-Peng; Fu, Shi-Tao; Tang, Xiang-Ying; Jiang, Min [Journal of Organic Chemistry, 2019, vol. 84, # 7, p. 4478 - 4485]

33
[ 14062-18-1 ]
[ 942-54-1 ]

Reference： [1]Journal of the American Chemical Society,1939,vol. 61,p. 3039
[2]Australian Journal of Chemistry,1967,vol. 20,p. 1413 - 1428

34
[ 14062-18-1 ]
[ 4052-30-6 ]
3-(4-methanesulfonylphenyl)-2-(4-methoxyphenyl)-3-oxo-propionic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With sodium hydride; 1,1'-carbonyldiimidazole; In DMF (N,N-dimethyl-formamide); at 20℃; for 12h;	Example 1; [ 3- (4-METHANESULFONYLPHENYL)-2- (4-METHOXYPHENYL)-3-OXO-PROPIONIC] acid ethyl ester. 1g of [4-METHANESULFONY] benzoicacid, 970mg of [4-METHOXYPHENYLACETIC] acid ethyl ester, and 950mg of carbonyldiimidazole were dissoved in [15MUT] of [DIMETHYLFORMAMIDE] and 230mg of sodium hydride were added dropwise to the solution and the mixture was reacted in room temperature for 12 hours. Afterwards, water was added to diute the resultant, followed by extraction with ethyl acetate. The obtained organic layer was dried over anhydrous magnesium sulfate to give 1.5g of the title compound as a light yellow liquid (yield 83%).
83%	With sodium hydride; 1,1'-carbonyldiimidazole; In DMF (N,N-dimethyl-formamide); at 20℃; for 12h;	1 g of 4-methanesulfony benzoicacid, 970 mg of 4-methoxyphenylacetic acid ethyl ester, and 950 mg of carbonyldiimidazole were dissoved in 15 ml of dimethylformamide and 230 mg of sodium hydride were added dropwise to the solution and the mixture was reacted in room temperature for 12 hours. Afterwards, water was added to diute the resultant, followed by extraction with ethyl acetate. The obtained organic layer was dried over anhydrous magnesium sulfate to give 1.5 g of the title compound as a light yellow liquid(yield 83%).

Reference： [1]Patent: WO2004/206,2003,A2 .Location in patent: Page 11
[2]Patent: US2004/2532,2004,A1 .Location in patent: Page 4-5

35
[ 3913-23-3 ]
[ 14062-18-1 ]
C₁₉H₂₁NO₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hexamethyldisilazane; In tetrahydrofuran; at -70 - 20℃; for 16h;	EXAMPLE 7; 5-(2-furyl)-4-[2-(2-methoxy-5-nitrophenyl)-1-(4-methoxyphenyl)ethyl-1,3-thiazol-2-amine; Step A; NaHMDS (30.0 mL, 30.0 mmol) was added to a -70C solution of ethyl 4-methoxyphenyl acetate (5.83 g, 30.0 mmol) and <strong>[3913-23-3]2-methoxy-5-nitrobenzyl bromide</strong> (7.38 g, 30.0 mmol) in 200 mL of THF. The reaction mixture was stirred to rt over a period of 16 h after which time the solvent was evaporated and the residue partitioned between 150 mL of EtOAc and 20 mL of saturated ammonium chloride. The aqueous phase was washed 2 x 25 mL of EtOAc and the combined organic extracts were washed with brine (20 mL) and dried over MgS04. The organic phase was dried, concentrated and chromatographed (0-50% EtOAc/hexane) to afford the monoalkylated target.

Reference： [1]Patent: WO2005/97767,2005,A1 .Location in patent: Page/Page column 39-41

36
[ 70258-18-3 ]
[ 14062-18-1 ]
[ 1263285-58-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hexamethyldisilazane In tetrahydrofuran at -70 - 20℃; for 16h;	4.A EXAMPLE 4; N'-{5-[2-(amino-1,3-thiazol-4-yl)-2-(4-methoxyphenyl)ethyl]pyridin-2-yl}, N-N-dimethylethane-1,2- diamine; Step A; NaHMDS (8.0 mL, 8.0 mmol) was added to a -70° C solution of ethyl 4-methoxyphenyl acetate (1.55 g, 8.0 mmol) and 2-chloro-5-chloromethylpyridine (1.29 g, 8.0 mmol) in 25 mL of THF. The reaction mixture was stirred to rt over a period of 16 h after which time the solvent was evaporated and the residue partitioned between 20 mL of EtOAc and 20 mL of saturated ammonium chloride. The aqueous phase was washed 2 x 25 mL of EtOAc and the combined organic extracts were washed with brine (20 mL) and dried over MgS04. Evaporation of the solvent left the monoalkylated target as a colorless oil.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2005/97767, 2005, A1 Location in patent: Page/Page column 35-37

37
[ 104-01-8 ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid; sodium hydrogencarbonate In ethanol; dichloromethane; water	1 Preparation of ethyl p-methoxyphenylacetate (IV; R=Et) Example 1 Preparation of ethyl p-methoxyphenylacetate (IV; R=Et) 10 g (0.06 mol) of p-methoxyphenylacetic acid, 30 ml (0.74 mol) of ethanol and 0.11 ml (0.0026 mol) of sulfuric acid were mixed in a 250 ml balloon flask provided with thermometer and reflux cooler. The thus obtained solution was heated to reflux (78° C.) and held for 1 hour 20 minutes. It was then cooled down at room temperature and 50 ml of deionized water were added. The ethanol was evaporated under vacuum and 40 ml of dichloromethane were added over the residual aqueous phase. The thus obtained mixture was stirred and allowed to decant. The organic phase was washed with 30 ml of a sodium bicarbonate saturated solution, was dried and filtered under vacuum. After evaporating the dichloromethane under vacuum, a colorless residue of ethyl p-methoxyphenylacetate weighing 10.41 g was obtained (Yield: 89%)
		3 Ethyl p-chlorophenylacetate Substituting p-methoxyphenylacetic acid for p-chlorophenylacetic acid and using the same manner as described above, ethyl p-methoxyphenylacetate was prepared.

Reference： [1]Current Patent Assignee: MEDICHEM, S.A. - US6506941, 2003, B1
[2]Current Patent Assignee: SHIONOGI & CO., LTD. - US5082947, 1992, A Current Patent Assignee: SHIONOGI & CO., LTD. - EP220025, 1991, B1

38
[ 14062-18-1 ]
[ 679788-76-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium In Diethyl carbonate	14.b b) b) Preparation of Ethyl 4-methoxyphenyl Malonate A mixture of ethyl 4-methoxyphenylacetate (27.8 g) and sodium (3.68 g) in 90 ml of diethylcarbonate is refluxed for 3 hours, then the solvent is evaporated under reduced pressure and the residue is diluted with water and neutralized with acetic acid. The aqueous phase is extracted twice with diethyl ether. The organic extracts are pooled and washed twice with 1 N sodium hydroxide and once with water, then the organic phase is dried over sodium sulfate and concentrated to dryness. 34.2 g of the product are obtained.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US6110924, 2000, A

39
[ 14062-18-1 ]
[ 57676-49-0 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrazine hydrate; In methanol;	Step 1: Preparation of (4-methoxyphenyl)acetic acid hydrazide. Hydrazine hydrate (4.7 cm3) was added dropwise to ethyl (4-methoxyphenyl)acetate (3.73 g) and then methanol (20 cm3) was added to form a homogeneous reaction mixture. This mixture was stirred for 18 hours at ambient temperature during which time a white precipitate formed. The precipitate was isolated by filtration and washed with methanol and water, then air-dried to give (4-methoxyphenyl)acetic acid hydrazide (2 g). M+ =180; 1 H NMR: delta 3.50(2H,s); 3.80(3H,s); 3.85(2H,br s); 6.70(1H,br s); 6.90(2H,d); 7.20(2H,d); (solid).

Reference： [1]Patent: US5705516,1998,A
[2]Chinese Journal of Chemistry,2010,vol. 28,p. 605 - 612
[3]European Journal of Medicinal Chemistry,2017,vol. 139,p. 263 - 279

40
diethyl 1-(p-methoxyphenyl)-1,2-cyclopropanedicarboxylate [ No CAS ]
[ 14062-18-1 ]
[ 344246-93-1 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; potassium hydroxide In ethanol	20 1-(p-Methoxyphenyl)-3-azabicyclo[3.1.0]hexane hydrochloride EXAMPLE 20 1-(p-Methoxyphenyl)-3-azabicyclo[3.1.0]hexane hydrochloride A mixture of 2.6 g. of diethyl 1-(p-methoxyphenyl)-1,2-cyclopropanedicarboxylate (prepared by the method of Example 5 from ethyl-p-methoxyphenylacetate), 20 ml. of 1 N potassium hydroxide and 20 ml. of ethanol is refluxed 3.5 hours and the ethanol is removed by concentrating. A 20 ml. portion of 1 N hydrochloric acid is added and then incremental portions of acid are added until the pH is one. The mixture is extracted three times with chloroform, dried and concentrated to a yellow solid. This solid is recrystallized from ethyl acetate-hexane to give cis-1-(p-methoxyphenyl)-1,2-cyclopropanedicarboxylic acid as a pale yellow solid.
	With hydrogenchloride; potassium hydroxide In ethanol	24 Preparation of 1-(p-Methoxyphenyl)-3-azabicyclo[3.1.0]hexane hydrochloride EXAMPLE 24 Preparation of 1-(p-Methoxyphenyl)-3-azabicyclo[3.1.0]hexane hydrochloride A mixture of 2.6 g of diethyl 1-(p-methoxyphenyl)-1,2-cyclopropanedicarboxylate (prepared by the method of Example 6 from ethyl-p-methoxyphenylacetate), 20 ml of 1N potassium hydroxide and 20 ml of ethanol is refluxed 3.5 hours and the ethanol is removed by concentrating. A 20 ml portion of 1N hydrochloric acid is added and then incremental portions of acid are added until the pH is one. The mixture is extracted three times with chloroform, dried and concentrated to a yellow solid. This solid is recrystallized from ethyl acetate-hexane to give cis-1-(p-methoxyphenyl)-1,2-cyclopropanedicarboxylic acid as a pale yellow solid.

Reference： [1]Current Patent Assignee: PFIZER INC - US4435419, 1984, A
[2]Current Patent Assignee: PFIZER INC - US4131611, 1978, A

41
[ 14062-18-1 ]
[ 68840-64-2 ]

Yield	Reaction Conditions	Operation in experiment
	With Hg; sodium In ethanol	4 2-(α-ethoxycarbonyl-4-methoxybenzylidene)-1-methylperhydroazepine EXAMPLE 4 2-(α-ethoxycarbonyl-4-methoxybenzylidene)-1-methylperhydroazepine Follow the procedure of Example 2 to obtain 15.6 g (34% of theory) of the title compound as a viscous yellow oil with a BP of 165° (0.001 mm of Hg) from 53.2 g of the title compound of Example 1, 29.1 g of ethyl 4-methoxyphenylacetate and a solution of 4.6 g of sodium in 100 ml of ethanol.

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US4221788, 1980, A

42
[ 14062-18-1 ]
[ 105942-08-3 ]
C₁₈H₁₆BrNO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium <i>tert</i>-butylate In 1-methyl-pyrrolidin-2-one at 10 - 20℃;	XXIII Example XXIII; 1-Bromo-4-cvano-3-(4-methoxy-benzyl)-benzene; A mixture of 25 g of ethyl (4-methoxy-phenyl)-acetate, 27.4 g of 1-bromo-4-cyano-3-fluoro- benzene and 20 mL of N-methyl-pyrrolidin-2-one is slowly added to 31.4 g of potassium tert butoxide in 130 mL of N-methyl-pyrrolidin-2-one keeping the temperature below 10°C. After stirring for 1 hour at room temperature, 100 mL of methanol and 137 mL of 1 M aqueous sodium hydroxide are added and the mixture is stirred overnight at room temperature. The methanol fraction is evaporated, the residue is basified with 1 M aqueous sodium hydroxide and extracted with tert butyl-methyl ether. The aqueous phase is acidified with 4 M hydrochloric acid and extracted with ethyl acetate several times. The combined ethyl acetate extracts are evaporated and the residue together with 120 mL of N,N-dimethyl formamide and 24.9 g of potassium carbonate heated at 100°C for 1 hour. The reaction mixture is diluted with aqueous sodium bicarbonate and extracted several times with ethyl acetate. The combined extracts are evaporated and the residue crystallized from methanol.Yield: 13 g (33% of theory)Mass spectrum (ESI+): m/z = 319/321 (Br) [IVH-NH4] +

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - WO2007/93610, 2007, A1 Location in patent: Page/Page column 48

43
[ 104-01-8 ]
[ 75-03-6 ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
86%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In benzene at 20℃; for 2h;

Reference： [1]Location in patent: experimental part Sadeghian, Hamid; Attaran, Neda; Jafari, Zeinab; Saberi, Mohammad Reza; Pordel, Mehdi; Riazi, Mohammad Mahdi [Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 6, p. 2327 - 2335]

44
[ 14062-18-1 ]
[ 7338-94-5 ]
[ 1172584-19-8 ]

Yield	Reaction Conditions	Operation in experiment
77%	Stage #1: ethyl p-methoxyphenylacetate With sodium hydride; dimethyl sulfoxide In mineral oil at 20℃; for 0.25h; Stage #2: 1,3-diphenyl-2-propynone In dimethyl sulfoxide; mineral oil at 20℃; Stage #3: With hydrogenchloride In water; dimethyl sulfoxide; mineral oil

Reference： [1]Location in patent: experimental part Shankar, Ravi; Chakravarti, Bandana; Singh, Uma Sharan; Ansari, Mohd. Imran; Deshpande, Shreekant; Dwivedi, Shailendra Kumar Dhar; Bid, Hemant Kumar; Konwar, Rituraj; Kharkwal, Geetika; Chandra, Vishal; Dwivedi, Anila; Hajela [Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 11, p. 3847 - 3856]

45
[ 14062-18-1 ]
[ 20442-66-4 ]
[ 15209-27-5 ]

Yield	Reaction Conditions	Operation in experiment
75%	Stage #1: ethyl p-methoxyphenylacetate With sodium hydride; dimethyl sulfoxide In mineral oil at 20℃; for 0.25h; Stage #2: 3-(4-methoxyphenyl)-1-phenylprop-2-yn-1-one In dimethyl sulfoxide; mineral oil at 20℃; Stage #3: With hydrogenchloride In water; dimethyl sulfoxide; mineral oil

Reference： [1]Location in patent: experimental part Shankar, Ravi; Chakravarti, Bandana; Singh, Uma Sharan; Ansari, Mohd. Imran; Deshpande, Shreekant; Dwivedi, Shailendra Kumar Dhar; Bid, Hemant Kumar; Konwar, Rituraj; Kharkwal, Geetika; Chandra, Vishal; Dwivedi, Anila; Hajela [Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 11, p. 3847 - 3856]

46
[ 14062-18-1 ]
[ 16616-43-6 ]
[ 143326-38-9 ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: ethyl p-methoxyphenylacetate With sodium hydride; dimethyl sulfoxide In mineral oil at 20℃; for 0.25h; Stage #2: 1-(4-methoxy-phenyl)-3-phenyl-propynone In dimethyl sulfoxide; mineral oil at 20℃; Stage #3: With hydrogenchloride In water; dimethyl sulfoxide; mineral oil

Reference： [1]Location in patent: experimental part Shankar, Ravi; Chakravarti, Bandana; Singh, Uma Sharan; Ansari, Mohd. Imran; Deshpande, Shreekant; Dwivedi, Shailendra Kumar Dhar; Bid, Hemant Kumar; Konwar, Rituraj; Kharkwal, Geetika; Chandra, Vishal; Dwivedi, Anila; Hajela [Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 11, p. 3847 - 3856]

47
[ 17138-28-2 ]
[ 77-78-1 ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
74%	With potassium carbonate In acetonitrile at 80℃; for 2h; Inert atmosphere;	To a stirred solution of ethyl 2-(4-hydroxyphenyl)acetate (10 g, 0.05 mol) in acetonitrile(100 mL) were added K2CO3 (15.3 g, 0.11 mol) and dimethyl sulfate (8.4 g, 0.06 mol) under an inert atmosphere. The reaction mixture was stirred at 80 0C for 2 h and then extracted with EtOAc (2 x 300 mL), The combined organic layers were washed with water, dried over Na2SO4 and concentrated in vacuo to afford ethyl 2-(4-methoxyphenyl) acetate (8 g, 74 %) as a white solid.

Reference： [1]Current Patent Assignee: FORUM PHARMACEUTICALS INC - WO2009/158393, 2009, A1 Location in patent: Page/Page column 60-61

48
[ 14062-18-1 ]
[ 6343-93-7 ]

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2010,vol. 49,p. 1499 - 1508

49
[ 104-92-7 ]
[ 105-53-3 ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
94%	With potassium phosphate; 18-crown-6 ether; bis(dibenzylideneacetone)-palladium⁽⁰⁾; tri tert-butylphosphoniumtetrafluoroborate at 160℃; for 12h; Inert atmosphere;
75%	With C₁₉H₂₃N₃O₂; copper(l) chloride; sodium t-butanolate In ethanol at 80℃; for 36h; Inert atmosphere; Schlenk technique;

Reference： [1]Song, Bingrui; Rudolphi, Felix; Himmler, Thomas; Goossen, Lukas J. [Advanced Synthesis and Catalysis, 2011, vol. 353, # 9, p. 1565 - 1574]
[2]Cheng, Fei; Chen, Tao; Huang, Yin-Qiu; Li, Jia-Wei; Zhou, Chen; Xiao, Xiao; Chen, Fen-Er [Organic Letters, 2022, vol. 24, # 1, p. 115 - 120]

50
[ 1161274-19-6 ]
[ 14062-18-1 ]
[ 1208331-31-0 ]

Yield	Reaction Conditions	Operation in experiment
40 g	Stage #1: ethyl p-methoxyphenylacetate With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.25h; Inert atmosphere; Stage #2: 4-cyano-2-methylbenzoyl chloride In tetrahydrofuran at -78 - 20℃; Inert atmosphere;	Synthesis of ethyl 3-(4-cyano-2-methylphenyl)-2-(4-methoxyphenyl)-3-oxopropanoate 5: General procedure: To a solution of (4-methoxy-phenyl)-acetic acid ethyl ester (25.96 g, 133.7 mmol) in anhydrous tetrahydrofuran (200 ml) was added lithium hexamethyldisilazide (200 ml, 1 M) at -78 °C under nitrogen. After being stirred for 15 min., a solution of 4-cyano-2-methylbenzoyl chloride (24 g, 133.6 mmol) in anhydrous tetrahydrofuran (150 ml) was added dropwise, and the resulting mixture was stirred at room temperature overnight for 16 h. The reaction mixture was quenched by the addition of saturated aqueous ammonium chloride solution (200 ml), and the resultant mixture was extracted with ethyl acetate (100 mlx3). The combined organic layers were dried over anhydrous sodium sulfate (20 g), filtered, and evaporated. The residue was purified on silica gel column (petroleum ether/ethyl acetate = 25:1) to give ethyl 3-(4-cyano-2-methylphenyl)-2-(4-methoxyphenyl)-3-oxopropanoate (40 g, yield 88.7%).

Reference： [1]Location in patent: experimental part Sun, Xicheng; Qiu, Jian; Strong, Sarah A.; Green, Louis S.; Wasley, Jan W.F.; Colagiovanni, Dorothy B.; Mutka, Sarah C.; Blonder, Joan P.; Stout, Adam M.; Richards, Jane P.; Chun, Lawrence; Rosenthal, Gary J. [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 12, p. 3671 - 3675]

51
[ 104-92-7 ]
[ 6148-64-7 ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
95%	With dmap; bis(η3-allyl-μ-chloropalladium(II)); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In 1,3,5-trimethyl-benzene at 140℃; for 20h; Inert atmosphere;	4.2. Pd-catalyzed decarboxylative cross-couplings of potassium malonate monoesters with aryl halides General procedure: after standard cycles of evacuation and back-filling with dry and pure nitrogen, an oven-dried Schlenk tube equipped with a magnetic stirring bar was charged with Pd source (see Table 1, Table 2, Table 3 and Table 4), ligand (see Table 1, Table 2, Table 3 and Table 4), N,N-dimethylpyridin-4-amine (DMAP, see Table 1, Table 2, Table 3 and Table 4), and ethyl potassium malonate (see Table 1, Table 2, Table 3 and Table 4). The tube was evacuated and backfilled with argon (this procedure was repeated three times). Under a counter flow of argon, aryl halide (see Table 1, Table 2, Table 3 and Table 4) and solvent (see Table 1, Table 2, Table 3 and Table 4) were added by syringe. The tube was sealed and stirred at room temperature for 10 min. Then the tube was connected to the Schlenk line, which was full of argon, stirred in a preheated oil bath (140-150 °C) for the appointed time (20-25 h). Upon completion of the reaction, the mixture was cooled to room temperature and diluted with diethyl ether, and the yields were determined by gas chromatography using 1,3-dimethoxybenzene as the internal standard.

Reference： [1]Location in patent: experimental part Feng, Yi-Si; Wu, Wei; Xu, Zhong-Qiu; Li, Yan; Li, Ming; Xu, Hua-Jian [Tetrahedron, 2012, vol. 68, # 9, p. 2113 - 2120]

52
[ 623-12-1 ]
[ 6148-64-7 ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
88%	With dmap; bis(η3-allyl-μ-chloropalladium(II)); ruphos In 1,3,5-trimethyl-benzene at 140℃; for 20h; Inert atmosphere;	4.2. Pd-catalyzed decarboxylative cross-couplings of potassium malonate monoesters with aryl halides General procedure: after standard cycles of evacuation and back-filling with dry and pure nitrogen, an oven-dried Schlenk tube equipped with a magnetic stirring bar was charged with Pd source (see Table 1, Table 2, Table 3 and Table 4), ligand (see Table 1, Table 2, Table 3 and Table 4), N,N-dimethylpyridin-4-amine (DMAP, see Table 1, Table 2, Table 3 and Table 4), and ethyl potassium malonate (see Table 1, Table 2, Table 3 and Table 4). The tube was evacuated and backfilled with argon (this procedure was repeated three times). Under a counter flow of argon, aryl halide (see Table 1, Table 2, Table 3 and Table 4) and solvent (see Table 1, Table 2, Table 3 and Table 4) were added by syringe. The tube was sealed and stirred at room temperature for 10 min. Then the tube was connected to the Schlenk line, which was full of argon, stirred in a preheated oil bath (140-150 °C) for the appointed time (20-25 h). Upon completion of the reaction, the mixture was cooled to room temperature and diluted with diethyl ether, and the yields were determined by gas chromatography using 1,3-dimethoxybenzene as the internal standard.

Reference： [1]Location in patent: experimental part Feng, Yi-Si; Wu, Wei; Xu, Zhong-Qiu; Li, Yan; Li, Ming; Xu, Hua-Jian [Tetrahedron, 2012, vol. 68, # 9, p. 2113 - 2120]

53
[ 104-93-8 ]
[ 64-17-5 ]
[ 201230-82-2 ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
85%	With di-tert-butyl peroxide; dichloro[4,5-bis(diphenylphosphino)-9,9’-dimethylxanthene]palladium(II) at 120℃; for 16h;	11 Preparation of p-Methoxyphenylacetic Acid from p-Methoxy Toluene and Ethanol p-Methoxy toluene (1.83 g), ethanol (46 mg), di-tert-butyl peroxide (73 mg, 1 equivalent), and Pd(Xantphos)Cl2 (3.8 mg, 1 mol %) were added into a reaction kettle, into which 10 atm carbon monoxide was introduced. The reaction was heated to 120° C., and stirred at this constant temperature for 16 h. After the reaction was completed, carbon monoxide was discharged, and 82 mg ethyl p-methoxyphenylacetate was obtained by column chromatography, in a yield of 85%. 1HNMR (400 MHz, CDCl3) δ 1.23 (t, J=6.8 Hz, 3H), 3.54 (s, 2H), 3.79 (s, 3H), 4.11 (q, J=6.8 Hz, 2H), 6.84-6.88 (m, 2H), 7.18-7.22 (m, 2H); 13CNMR (100 MHz, CDCl3) δ 14.2, 40.5, 55.3, 60.8, 113.9, 126.3, 130.3, 158.7, 171.9; HRMS (ESI) calcd. for C11H14NaO3 [M+Na]: 217.0835. found: 217.0838. The ethyl p-methoxyphenylacetate obtained was dissolved in 1,4-dioxane. 6 N sodium hydroxide solution was added, and the reaction was heated to 60° C. After 2 h of reaction, the pH value was adjusted to 1 by adding 2 N hydrochloric acid. After removing the organic solvent under reduced pressure, 64 mg product p-methoxyphenylacetic acid was obtained by extraction with ethyl acetate, and the yield of hydrolysis was 91%.
66%	With di-tert-butyl peroxide; dichloro[4,5-bis(diphenylphosphino)-9,9’-dimethylxanthene]palladium(II) at 120℃; for 16h; Inert atmosphere;

Reference： [1]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES - US2013/303798, 2013, A1 Location in patent: Paragraph 0048; 0049
[2]Xie, Pan; Xie, Yinjun; Qian, Bo; Zhou, Han; Xia, Chungu; Huang, Hanmin [Journal of the American Chemical Society, 2012, vol. 134, # 24, p. 9902 - 9905]

54
[ 14062-18-1 ]
[ 107445-17-0 ]

Yield	Reaction Conditions	Operation in experiment
75%	With 4-acetamidobenzenesulfonyl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20℃; for 16h; Inert atmosphere;	3. General procedure B for the synthesis of α-aryl-α-diazoacetates General procedure: To the stirred solution propargyl α-(4-methoxyphenyl)acetate 6a (2.04 g, 10 mmol) in 15 mL acetonitrile was added 4-acetamidobenzenesulfonyl azide (2.88 g, 12 mmol) and DBU (2.24 mL, 15 mmol) at ambient temperature under inert atmosphere. The reaction mixture was stirred for 16 h at room temperature. The reaction was quenched with saturated NH4Cl and the product was extracted with diethyl ether (30 mL x 3). The combined organic layers were washed with brine and dried over anhydrous Na2SO4. The extract was filtered and the filtrate was evaporated under vacuum. The crude product was purified using column chromatography over silica gel to afford propargyl α-(4-methoxyphenyl)-α-diazoacetate 1a as orange solid (1.934 g, 84% yield).
48%	With 4-acetamidobenzenesulfonyl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 0 - 25℃; for 24h; Inert atmosphere;
	With 4-toluenesulfonyl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20℃;

	With 4-toluenesulfonyl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20℃; for 15h;
	With 4-toluenesulfonyl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene at 20℃; for 15h;
	With 4-toluenesulfonyl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20℃;
	With 4-acetamidobenzenesulfonyl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 0 - 20℃; Inert atmosphere;	4.4.3.2. Synthesis of 2-aryl-2-diazo-acetate esters. General procedure: All the diazo reagents except for the commercially available ethyl2-diazo-acetate (EDA) used for preparation of 16 and 17 were prepared according to the following method. The appropriate 2-aryl-acetate ester from Section 4.4.3.1. (1 equiv) and para-acetamido-benzene-sulfonyl azide (1.2 equiv) were dissolved inacetonitrile (10 mL) and cooled to 0 C under nitrogen atmosphere.Then, DBU (1.5 equiv) was added dropwise under stirring. The mixture was stirred overnight at room temperature. The solvent was evaporated under reduced pressure and the residue was extracted with ethyl acetate (2 20 mL). The organic layer was furtherwashed with brine (10 mL), dried with Na2SO4, concentrated underreduced pressure and crude was purified via flash chromatography using a ethyl acetate-hexanes mixture (1:9).
	With 4-toluenesulfonyl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 0 - 20℃; Inert atmosphere;
	With 4-toluenesulfonyl azide In acetonitrile
	With 4-toluenesulfonyl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20℃; for 15h;
	With 4-toluenesulfonyl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20℃;
	With 4-toluenesulfonyl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20℃; Inert atmosphere; Schlenk technique;
	With 4-toluenesulfonyl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 40℃; for 1h; Microwave irradiation;
	With 4-acetamidobenzenesulfonyl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20℃; for 12h; Inert atmosphere;
	With 4-acetamidobenzenesulfonyl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 0 - 23℃; Inert atmosphere;

Reference： [1]Navale, Balu S.; Laha, Debasish; Bhat, Ramakrishna G. [Tetrahedron Letters, 2019, vol. 60, # 29, p. 1899 - 1903]
[2]Davis, Owen A.; Croft, Rosemary A.; Bull, James A. [Chemical Communications, 2015, vol. 51, # 84, p. 15446 - 15449]
[3]Hu, Mingyou; Ni, Chuanfa; Hu, Jinbo [Journal of the American Chemical Society, 2012, vol. 134, # 37, p. 15257 - 15260]
[4]Hu, Mingyou; Ni, Chuanfa; Li, Lingchun; Han, Yongxin; Hu, Jinbo [Journal of the American Chemical Society, 2015, vol. 137, # 45, p. 14496 - 14501]
[5]Luo, Xuesong; Chen, Gui; He, Lin; Huang, Xueliang [Journal of Organic Chemistry, 2016, vol. 81, # 7, p. 2943 - 2949]
[6]Hu, Mingyou; Xie, Qiqiang; Li, Xinjin; Ni, Chuanfa; Hu, Jinbo [Chinese Journal of Chemistry, 2016, vol. 34, # 5, p. 469 - 472] Chen, Lin; Cui, Yu-Sheng; Duan, Xiu; Guo, Kai; Qin, Long-Zhou; Qiu, Jiang-Kai; Sun, Qi; Yuan, Xin; Zhuang, Kai-Qiang [Advanced Synthesis and Catalysis, 2020, vol. 362, # 22, p. 5093 - 5104]
[7]Tyagi, Vikas; Alwaseem, Hanan; O'Dwyer, Kristen M.; Ponder, Jessica; Li, Qi Ying; Jordan, Craig T.; Fasan, Rudi [Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 17, p. 3876 - 3886]
[8]Hu, Xiao-Qian; Han, Jia-Bin; Zhang, Cheng-Pan [European Journal of Organic Chemistry, 2017, vol. 2017, # 2, p. 324 - 331]
[9]Rao, Santhosh; Prabhu, Kandikere Ramaiah [Organic Letters, 2017, vol. 19, # 4, p. 846 - 849]
[10]Rao, Changqing; Mai, Shaoyu; Song, Qiuling [Chemical Communications, 2018, vol. 54, # 47, p. 5964 - 5967]
[11]San, Htet Htet; Wang, Shi-Jun; Jiang, Min; Tang, Xiang-Ying [Organic Letters, 2018, vol. 20, # 15, p. 4672 - 4676]
[12]San, Htet Htet; Wang, Chun-Ying; Zeng, Hai-Peng; Fu, Shi-Tao; Tang, Xiang-Ying; Jiang, Min [Journal of Organic Chemistry, 2019, vol. 84, # 7, p. 4478 - 4485]
[13]Huang, Fei; Huang, He; Hughes, Timothy; Xie, Yuxing; Xu, Jun; Yu, Yang; Zhang, Zhipeng [Green Chemistry, 2020, vol. 22, # 13, p. 4165 - 4173]
[14]Chu, Changhu; Dong, Wenwen; Lin, Jia; Teng, Jiangge; Wang, Zhiwei; Zhao, Rong [Organic and Biomolecular Chemistry, 2021, vol. 19, # 27, p. 6120 - 6126]
[15]Chen, Liang; Gao, Meng; Lu, Cuifen; Ma, Chao; Ruan, Mengyao; Wen, Ziyang; Yang, Fan; Yang, Guichun [Chemical Communications, 2022, vol. 58, # 13, p. 2168 - 2171]

55
[ 696-62-8 ]
[ 141-97-9 ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
76%	With potassium phosphate; copper(l) iodide; ethanol In dimethyl sulfoxide at 80℃; for 20h; Inert atmosphere;
33%	With caesium carbonate In 1,4-dioxane at 100℃; for 12h;	General procedure: General procedure: A mixture of aryl iodide (5 mmol), ethyl acetoacetate(7.5 mmol), Cu2+/4A (0.5 g, 0.1 mol % copper) and Cs2CO3 (12.5 mmol) indioxane (10 ml) was stirred at 100 C for 12 h. The solid was filtered and thefiltrate was evaporated in vacuo. The products were purified by columnchromatography (silica gel, hexane/acetone 4:1 eluent). The products werecharacterized by 1H NMR and GC-MS.

Reference： [1]Ke, Jie; He, Chuan; Liu, Huiying; Xu, Huan; Lei, Aiwen [Chemical Communications, 2013, vol. 49, # 60, p. 6767 - 6769]
[2]Zsolczai, Dávid; Németh, János; Hell, Zoltán [Tetrahedron Letters, 2015, vol. 56, # 46, p. 6389 - 6392]

56
[ 14062-18-1 ]
C₂₇H₂₃BrO₂ [ No CAS ]
[ 1454797-92-2 ]

Yield	Reaction Conditions	Operation in experiment
74%	Stage #1: ethyl p-methoxyphenylacetate With diisopropylamine In tetrahydrofuran; hexane at -78℃; for 0.25h; Inert atmosphere; Stage #2: C₂₇H₂₃BrO₂ In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere;	General procedure for the synthesis of ethyl 2,3,3-tris(4-(benzyloxy)-3-methoxyphenyl)propanoate (6aa') and NMR data of 6aa'-dg'. General procedure: N,N-Diisopropylamine (3.9 mmol) and THF (10 mL) were added to an oven dried 50 mL RB flask under N2 atm. The mixture was cooled to 0 °C. n-BuLi (3.85 mmol, 1.6 M solution in hexanes) was slowly added to the above solution under N2 atm then was stirred for 30 min at the same temperature. The flask was cooled to -78 °C and ester 5 (3.1 mmol) in THF (5 mL) was slowly added. The mixture was stirred for 15 min at the same temperature. Then, the intermediate bromo compound (0.77 mmol) in THF (5 mL) was added. The mixture was stirred at -78 °C for 30 min. On completion, the reaction mixture was allowed to warm to 0 °C, quenched with cold water and extracted into ethyl acetate. The organic layer was dried with anhydrous Na2SO4 and the volatiles were evaporated. The crude compound was purified by column chromatography (30% EtOAc/hexane) to afford compound 6aa'.

Reference： [1]Pericherla, Kasiviswanadharaju; Shirazi, Amir Nasrolahi; Kameshwara Rao; Tiwari, Rakesh K.; Dasilva, Nicholas; McCaffrey, Kellen T.; Beni, Yousef A.; Gonzalez-Sarrias, Antonio; Seeram, Navindra P.; Parang, Keykavous; Kumar, Anil [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 19, p. 5329 - 5331]

57
[ 14062-18-1 ]
[ 69545-37-5 ]
[ 1454797-97-7 ]

Yield	Reaction Conditions	Operation in experiment
58%	Stage #1: ethyl p-methoxyphenylacetate With diisopropylamine In tetrahydrofuran; hexane at -78℃; for 0.25h; Inert atmosphere; Stage #2: di(p-anisyl)methyl bromide In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere;	General procedure for the synthesis of ethyl 2,3,3-tris(4-(benzyloxy)-3-methoxyphenyl)propanoate (6aa') and NMR data of 6aa'-dg'. General procedure: N,N-Diisopropylamine (3.9 mmol) and THF (10 mL) were added to an oven dried 50 mL RB flask under N2 atm. The mixture was cooled to 0 °C. n-BuLi (3.85 mmol, 1.6 M solution in hexanes) was slowly added to the above solution under N2 atm then was stirred for 30 min at the same temperature. The flask was cooled to -78 °C and ester 5 (3.1 mmol) in THF (5 mL) was slowly added. The mixture was stirred for 15 min at the same temperature. Then, the intermediate bromo compound (0.77 mmol) in THF (5 mL) was added. The mixture was stirred at -78 °C for 30 min. On completion, the reaction mixture was allowed to warm to 0 °C, quenched with cold water and extracted into ethyl acetate. The organic layer was dried with anhydrous Na2SO4 and the volatiles were evaporated. The crude compound was purified by column chromatography (30% EtOAc/hexane) to afford compound 6aa'.

Reference： [1]Pericherla, Kasiviswanadharaju; Shirazi, Amir Nasrolahi; Kameshwara Rao; Tiwari, Rakesh K.; Dasilva, Nicholas; McCaffrey, Kellen T.; Beni, Yousef A.; Gonzalez-Sarrias, Antonio; Seeram, Navindra P.; Parang, Keykavous; Kumar, Anil [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 19, p. 5329 - 5331]

58
[ 64-17-5 ]
[ 768-60-5 ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
89%	With 4-methylpyridine-1-oxide; chloro(1,5-cyclooctadiene)rhodium(I) dimer; P(p-C₆H₄F)3 In acetonitrile at 60℃; for 2h; chemoselective reaction;
89%	With 4-methylpyridine-1-oxide; chloro(1,5-cyclooctadiene)rhodium(I) dimer; P(p-C₆H₄F)3 In acetonitrile at 60℃; for 2h;

Reference： [1]Kim, Insu; Lee, Chulbom [Angewandte Chemie - International Edition, 2013, vol. 52, # 38, p. 10023 - 10026][Angew. Chem., 2013, vol. 125, # 38, p. 10207 - 10210,4]
[2]Wang, Youliang; Zhang, Liming [Synthesis, 2015, vol. 46, # 4]

59
[ 14062-18-1 ]
[ 120-14-9 ]
C₂₀H₂₄O₆ [ No CAS ]
C₂₀H₂₄O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 55% 2: 13%	Stage #1: ethyl p-methoxyphenylacetate With n-butyllithium; diisopropylamine In tetrahydrofuran at -78℃; for 1h; Stage #2: 3,4-dimethoxy-benzaldehyde In tetrahydrofuran at -78℃; for 3h;	4.11 Diastereomeric 32E and 32T 4.11 Diastereomeric 32E and 32T (0048) A solution of diisopropylamine (8.9mL, 62.6mmol) in dry THF (90mL) containing 25mL (62.6mmol) of 2.5M n-BuLi at -78°C and stirred for 30min. Acetate ester 30 (12.2g, 62.6mmol) was added dropwise and the resulting solution was stirred over for 1h followed by addition of veratrylaldehyde 18 (8.0g, 48.1mmol). After 3h additional stirring at the same temperature, the mixture was diluted with H2O and extracted with EtOAc. The organic layer was dried and evaporated in vacuo to give a residue, which was subjected to column chromatography (EtOAc/hexane 1:3) to yield erythro 32E (9.5g, 55%) and 32T (2.3g, 13%). 4.11.1 32E (l) (0049) 1H NMR (CDCl3) δ 1.21 (t, 3H, J=7Hz), 3.03 (s, 1H) 3.71 (s, 3H), 3.72 (s, 3H), 3.73-3.75 (m, 1H), 3.78 (s, 3H), 4.11-4.23 (m, 2H), 5.06 (d, 1H, J=8Hz), 6.58-6.65 (m, 3H), 6.69 (d, 2H, J=8.5Hz), 6.97 (d, 2H, J=8.5Hz); 13C NMR (CDCl3) δ 14.0, 55.1, 55.7, 55.7, 59.3, 61.1, 76.4, 109.4, 110.4, 113.8, 118.9, 127.5, 129.6, 131.0, 133.4, 148.3, 148.4, 158.8, 173.7; HRMS (ES) m/z 383.1458 (M+Na, C20H24O6Na requires 383.1471). 4.11.2 32T (sol mp 132°C) (0050) 1H NMR (CDCl3) δ 1.06 (t, 3H, J=7Hz), 3.72 (d, 1H, J=4.5Hz), 3.78 (s, 6H), 3.85 (s, 3H), 3.92-4.05 (m, 2H), 5.18 (d, 1H, J=7.5Hz), 6.74 (s, 1H), 6.78 (d, 1H, J=8Hz), 6.84-6.86 (m, 3H), 7.25 (d, 2H, J=7.5Hz); 13C NMR (CDCl3) δ 13.9, 55.2, 55.7, 55.8, 58.8, 60.8, 74.9, 109.7, 110.5, 113.9, 119.0, 126.7, 130.2, 133.4, 148.5, 148.5, 159.2, 172.7; HRMS (ES) m/z 383.1473 (M+Na, C20H24O6Na requires 383.1471).

Reference： [1]Lim, Suk Hyun; Lee, Woo Sol; Kim, Young-Il; Sohn, Youngku; Cho, Dae Won; Kim, Cheolhee; Kim, Eunae; Latham, John A.; Dunaway-Mariano, Debra; Mariano, Patrick S. [Tetrahedron, 2015, vol. 71, # 24, p. 4236 - 4247]

60
[ 14062-18-1 ]
[ 124840-93-3 ]
C₁₇H₁₄O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	Stage #1: ethyl p-methoxyphenylacetate With lithium diisopropyl amide In tetrahydrofuran; hexane; ethylbenzene at -78℃; for 0.75h; Inert atmosphere; Stage #2: (S)-(+)-5-phenyl-1,3-dioxolane-2,4-dione In tetrahydrofuran; hexane; ethylbenzene at -78 - 20℃; for 2h; Inert atmosphere;	3.2.16 General procedure for the synthesis of compounds 14a-h General procedure: A solution of the appropriate aryl acetates 11-13 (4 mmol) in THF (2 mL) was added drop wise via a syringe over a period of 10 min to a solution of lithium diisopropylamide (LDA) 2.0 M solution in THF/hexane/ethylbenzene (4 mmol, 2 ml) in THF (10 mL) at -78 °C under nitrogen. The mixture was stirred for 45 min, then the appropriate 1,3-dioxolane-2,4-dione (6c-d) (2.0 mmol) in THF (2 mL) was added drop wise over 10 min. The reaction mixture was stirred for 1 h at -78 °C and 1 h at room temperature, quenched with water (5 mL), and the THF evaporated in vacuum. The resulting aqueous layer was then washed with Et2O (15 mL) and acidified with HCl 10% to pH=1-2 in an ice-water bath, to give the corresponding compounds (14a-e) as solid products, which were dried in vacuum over P2O5 for 2-3 h. Otherwise 14a-e were isolated by extraction of aqueous layer with CH2Cl2 (3×30 mL), the combined organic layers were dried over Na2SO4 and concentrated under reduced pressure, to give the final products.

Reference： [1]Prousis, Kyriakos C.; Markopoulos, John; Mckee, Vickie; Igglessi-Markopoulou, Olga [Tetrahedron, 2015, vol. 71, # 45, p. 8637 - 8648]

61
[ 14062-18-1 ]
[ 1333166-43-0 ]
C₁₈H₁₆O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	Stage #1: ethyl p-methoxyphenylacetate With lithium diisopropyl amide In tetrahydrofuran; hexane; ethylbenzene at -78℃; for 0.75h; Inert atmosphere; Stage #2: (S)-5-benzyl-1,3-dioxolane-2,4-dione In tetrahydrofuran; hexane; ethylbenzene at -78 - 20℃; for 2h; Inert atmosphere;	3.2.16 General procedure for the synthesis of compounds 14a-h General procedure: A solution of the appropriate aryl acetates 11-13 (4 mmol) in THF (2 mL) was added drop wise via a syringe over a period of 10 min to a solution of lithium diisopropylamide (LDA) 2.0 M solution in THF/hexane/ethylbenzene (4 mmol, 2 ml) in THF (10 mL) at -78 °C under nitrogen. The mixture was stirred for 45 min, then the appropriate 1,3-dioxolane-2,4-dione (6c-d) (2.0 mmol) in THF (2 mL) was added drop wise over 10 min. The reaction mixture was stirred for 1 h at -78 °C and 1 h at room temperature, quenched with water (5 mL), and the THF evaporated in vacuum. The resulting aqueous layer was then washed with Et2O (15 mL) and acidified with HCl 10% to pH=1-2 in an ice-water bath, to give the corresponding compounds (14a-e) as solid products, which were dried in vacuum over P2O5 for 2-3 h. Otherwise 14a-e were isolated by extraction of aqueous layer with CH2Cl2 (3×30 mL), the combined organic layers were dried over Na2SO4 and concentrated under reduced pressure, to give the final products.

Reference： [1]Prousis, Kyriakos C.; Markopoulos, John; Mckee, Vickie; Igglessi-Markopoulou, Olga [Tetrahedron, 2015, vol. 71, # 45, p. 8637 - 8648]

62
[ 14062-18-1 ]
(S)-5-isopropyl-1,3-dioxolane-2,4-dione [ No CAS ]
[ 238421-40-4 ]

Yield	Reaction Conditions	Operation in experiment
60%	Stage #1: ethyl p-methoxyphenylacetate With lithium diisopropyl amide In tetrahydrofuran; hexane; ethylbenzene at -78℃; for 0.75h; Inert atmosphere; Stage #2: (S)-5-isopropyl-1,3-dioxolane-2,4-dione In tetrahydrofuran; hexane; ethylbenzene at -78 - 20℃; for 2h; Inert atmosphere;	3.2.16 General procedure for the synthesis of compounds 14a-h General procedure: A solution of the appropriate aryl acetates 11-13 (4 mmol) in THF (2 mL) was added drop wise via a syringe over a period of 10 min to a solution of lithium diisopropylamide (LDA) 2.0 M solution in THF/hexane/ethylbenzene (4 mmol, 2 ml) in THF (10 mL) at -78 °C under nitrogen. The mixture was stirred for 45 min, then the appropriate 1,3-dioxolane-2,4-dione (6c-d) (2.0 mmol) in THF (2 mL) was added drop wise over 10 min. The reaction mixture was stirred for 1 h at -78 °C and 1 h at room temperature, quenched with water (5 mL), and the THF evaporated in vacuum. The resulting aqueous layer was then washed with Et2O (15 mL) and acidified with HCl 10% to pH=1-2 in an ice-water bath, to give the corresponding compounds (14a-e) as solid products, which were dried in vacuum over P2O5 for 2-3 h. Otherwise 14a-e were isolated by extraction of aqueous layer with CH2Cl2 (3×30 mL), the combined organic layers were dried over Na2SO4 and concentrated under reduced pressure, to give the final products.

Reference： [1]Prousis, Kyriakos C.; Markopoulos, John; Mckee, Vickie; Igglessi-Markopoulou, Olga [Tetrahedron, 2015, vol. 71, # 45, p. 8637 - 8648]

63
[ 14062-18-1 ]
[ 1446332-69-9 ]
C₂₅H₂₈N₂O₅ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 6070 - 6085

64
[ 623-73-4 ]
[ 100-66-3 ]
[ 35553-92-5 ]
[ 14062-18-1 ]
[ 6056-23-1 ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 6530 - 6534
Angew. Chem.,2016,vol. 128,p. 6640 - 6644,5
[2]Organometallics,2017,vol. 36,p. 172 - 179

65
[ 38205-60-6 ]
[ 14062-18-1 ]
5-[5-[(4-methoxyphenyl)methyl]-1H-pyrazol-3-yl]-2,4-dimethylthiazole [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 10163 - 10175

66
[ 38205-60-6 ]
[ 14062-18-1 ]
1-(2,4-dimethyl-1,3-thiazol-5-yl)-4-(4-methoxyphenyl)-butane-1,3-dione [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 10163 - 10175

67
[ 14062-18-1 ]
[ 768-60-5 ]
1,4-bis(4-methoxyphenyl)but-3-yn-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%	Stage #1: 4-methoxyphenylacetylen With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Stage #2: ethyl p-methoxyphenylacetate With boron trifluoride diethyl etherate In tetrahydrofuran; hexane at -78℃;

Reference： [1]Sadamitsu, Yuta; Komatsuki, Keiichi; Saito, Kodai; Yamada, Tohru [Organic Letters, 2017, vol. 19, # 12, p. 3191 - 3194]

68
[ 14062-18-1 ]
N-(4-methoxy-3,5-dibromophenyl)methoxycarbimide [ No CAS ]
N-(4-methoxy-3,5-dibromophenyl) 2-(4-methoxyphenyl)-2-ethoxycarbonylvinyl amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	Stage #1: N-(4-methoxy-3,5-dibromophenyl)methoxycarbimide With sodium methylate In methanol at 20℃; for 0.25h; Stage #2: ethyl p-methoxyphenylacetate With 4-methoxyphenyl acetate In methanol at 20℃; for 4h;	1.3 The N- (4-methoxy-3,5-dibromophenyl) methoxycarboximide was dissolved in 15 times the mass of anhydrous methanol, sodium methoxide added NaOMe was stirred at room temperature for 15min,Further ethyl 4-methoxyphenylacetate,N- (4-methoxy-3,5-dibromophenyl) methoxycarbimide,Sodium methoxide NaOMe and 4-methoxy phenyl acetate material amount ratio of 1: 1: 1, continue to react at room temperature, 4h,Methanol was evaporated, methanol was added with equal volume of water, stirred 10min, suction filtered and dried to give a white solidN- (4-methoxy-3,5-dibromophenyl) 2- (4-methoxyphenyl) -2-ethoxycarbonylvinyl amine;Yield 99%.
99%	Stage #1: N-(4-methoxy-3,5-dibromophenyl)methoxycarbimide With sodium methylate In methanol at 20℃; for 0.25h; Stage #2: ethyl p-methoxyphenylacetate In methanol at 20℃; for 4h;	1.3 (3) Dissolve N-(4-methoxy-3,5-dibromophenyl)carbodiimide in 15 times the mass of anhydrous methanol.After adding sodium methoxide NaOMe, stirring at room temperature for 15min, and then adding ethyl 4-methoxyphenylacetate,N-(4-methoxy-3,5-dibromophenyl)carbodiimide,The ratio of the sodium methoxide NaOMe to the 4-methoxy benzene ethyl acetate material is 1:1:1,Continue the reaction at room temperature for 4 h. Evaporate the methanol, add water equal to the volume of methanol, stir for 10 min, and filter by suction.Drying gave N-(4-methoxy-3,5-dibromophenyl)2-(4-methoxyphenyl)-2-ethoxycarbonylvinylamine as a white solid; yield 99%.
99%	Stage #1: N-(4-methoxy-3,5-dibromophenyl)methoxycarbimide With sodium methylate In methanol at 20℃; for 0.25h; Stage #2: ethyl p-methoxyphenylacetate In methanol at 20℃; for 3h;	1.3 (3) Dissolve N-(4-methoxy-3,5-dibromophenyl)carbodiimide in 15 times the mass of anhydrous methanol.After adding sodium methoxide NaOMe, stirring at room temperature for 15min, and then adding ethyl 4-methoxyphenylacetate,N-(4-methoxy-3,5-dibromophenyl)carbodiimide,The ratio of sodium methoxide NaOMe and 4-methoxybenzene ethyl acetate material is 1:1:1,Continue the reaction at room temperature for 4h. Evaporate the methanol, add water equal to the volume of methanol, stir for 10min, and filter by suction.Drying to give N-(4-methoxy-3,5-dibromophenyl)2-(4-methoxyphenyl)-2-ethoxycarbonylvinylamine as a white solid;Yield 99%;

Reference： [1]Current Patent Assignee: GUANGZHOU UNIVERSITY - CN107417612, 2017, A Location in patent: Paragraph 0019; 0029; 0031; 0034; 0041; 0049; 0056
[2]Current Patent Assignee: GUANGZHOU UNIVERSITY - CN107501175, 2017, A Location in patent: Paragraph 0029; 0032; 0039; 0047; 0054
[3]Current Patent Assignee: GUANGZHOU UNIVERSITY; NANJING UNIVERSITY - CN107501174, 2017, A Location in patent: Paragraph 0029; 0030; 0031; 0032; 0039; 0046; 0052

69
[ 14062-18-1 ]
[ 98-95-3 ]
[ 1151-94-6 ]

Yield	Reaction Conditions	Operation in experiment
80%	With potassium <i>tert</i>-butylate In benzene at 20℃; regiospecific reaction;

Reference： [1]Kumar, Promod; Sharma, Anup Kumar; Guntreddi, Tirumaleswararao; Singh, Rahul; Singh, Krishna Nand [Organic Letters, 2018, vol. 20, # 3, p. 744 - 747]

70
[ 14062-18-1 ]
[ 88-73-3 ]
(3-chloro-4-nitrophenyl)(4-methoxyphenyl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With potassium <i>tert</i>-butylate In benzene at 20℃; regiospecific reaction;

Reference： [1]Kumar, Promod; Sharma, Anup Kumar; Guntreddi, Tirumaleswararao; Singh, Rahul; Singh, Krishna Nand [Organic Letters, 2018, vol. 20, # 3, p. 744 - 747]

71
[ 99-08-1 ]
[ 14062-18-1 ]
(4-methoxyphenyl)(2-methyl-4-nitrophenyl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With potassium <i>tert</i>-butylate In benzene at 20℃; regiospecific reaction;

Reference： [1]Kumar, Promod; Sharma, Anup Kumar; Guntreddi, Tirumaleswararao; Singh, Rahul; Singh, Krishna Nand [Organic Letters, 2018, vol. 20, # 3, p. 744 - 747]

72
ethyl 2-(4-methoxyphenyl)-1,3-dithiane-2-carboxylate [ No CAS ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
91%	Stage #1: ethyl 2-(4-methoxyphenyl)-1,3-dithiane-2-carboxylate With chloro-trimethyl-silane; sodium iodide In dichloromethane at 20℃; for 15h; Inert atmosphere; Green chemistry; Stage #2: With chloro-trimethyl-silane; water; sodium iodide In dichloromethane at 20℃; Inert atmosphere; Green chemistry;

Reference： [1]Zhao, Guangkuan; Yuan, Ling-Zhi; Alami, Mouad; Provot, Olivier [Advanced Synthesis and Catalysis, 2018, vol. 360, # 13, p. 2522 - 2536]

73
ethyl 2,2-bis(ethylthio)-2-(4-methoxyphenyl)acetate [ No CAS ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
90%	Stage #1: ethyl 2,2-bis(ethylthio)-2-(4-methoxyphenyl)acetate With chloro-trimethyl-silane; sodium iodide In dichloromethane at 20℃; for 24h; Inert atmosphere; Green chemistry; Stage #2: With chloro-trimethyl-silane; water; sodium iodide In dichloromethane at 20℃; Inert atmosphere; Green chemistry;

Reference： [1]Zhao, Guangkuan; Yuan, Ling-Zhi; Alami, Mouad; Provot, Olivier [Advanced Synthesis and Catalysis, 2018, vol. 360, # 13, p. 2522 - 2536]

74
[ 14062-18-1 ]
H₂O₄S*C₉H₁₂FNO [ No CAS ]
[ 109-94-4 ]
[ 1092495-21-0 ]

Yield	Reaction Conditions	Operation in experiment
91.56%	Stage #1: ethyl p-methoxyphenylacetate; formic acid ethyl ester With sodium t-butanolate In 1,2-dimethoxyethane at 15 - 20℃; for 2h; Large scale; Stage #2: H₂O₄S*C₉H₁₂FNO With sodium carbonate In 1,2-dimethoxyethane; water at 5 - 70℃; for 2.5h; Large scale;	8 Preparation of 5-fluoro-3- (4-methoxyphenyl) -8-propoxy-1 H-quinolin-4-one 5.18 kg of sodium t-butoxide was added to 4-methoxyphenylacetic acid ethyl ester (8.36 kg), ethyl formate (4.57 kg) and 1,2-dimethoxyethane (50 L) at 20 ° C. or lower, and at 15 ± 5 ° C. And the mixture was stirred for 2 hours. After cooling the reaction solution to 5 ° C. or lower,A solution of sodium carbonate (1.11 kg) in water (10 L) and 5-fluoro-2-propoxyaniline sulfate (10.00 kg) were added and the mixture was stirred at 20 ° C. or less for 30 minutes and at 70 ± 5 ° C. for 2 hours. The reaction solution was cooled to room temperature and concentrated under reduced pressure. Toluene (60 L) and water (20 L) were added to the residue and the mixture was stirred and then allowed to stand and separated. After washing the organic layer with water and a solution of sodium hydrogen carbonate (0.47 kg) water (20 L), toluene was removed under atmospheric pressure. Diphenyl ether (15 L) was added to the residue, and the mixture was stirred at 240 to 245 ° C. for 5 hours. The reaction solution was cooled to 80 ° C., And ethyl acetate (30 L) were added and stirred. After the precipitate was formed, the mixture was stirred at 60 to 80 ° C. for 30 minutes. After cooling the reaction solution to room temperature, the precipitate was collected by filtration, washed with ethyl acetate and dried at 60 ° C. to give 5-fluoro-3- (4-methoxyphenyl) -8-propoxy- To obtain a 4-one crude product (11.21 kg, yield 91.56%).

Reference： [1]Current Patent Assignee: OTSUKA HOLDINGS CO LTD - JP2018/123072, 2018, A Location in patent: Paragraph 0113

75
[ 67-56-1 ]
[ 104-01-8 ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
88.54%	With sulfuric acid at 60 - 70℃; for 2h; Large scale;	3 Preparation of 4-methoxyphenylacetic acid ethyl ester 4-methoxyphenylacetic acid (15.00 kg), methanol (60 L) and sulfuric acid (0.44 kg) were stirred at 60 to 70 ° C. for 2 hours.After the reaction solution was cooled to room temperature,25% caustic soda solution (1.44 kg) was added and the mixture was concentrated under reduced pressure.Toluene (60 L) and water (7.5 L) were added to the residue and the mixture was stirred,Standing and liquid separation.A 25% caustic soda solution (0.72 kg) and water (7.5 L) were added to the organic layer, and the mixture was stirred and then allowed to stand and liquid.After washing the organic layer with water,And concentrated under reduced pressure to give ethyl 4-methoxyphenylacetate (15.52 kg, yield 88.54%).

Reference： [1]Current Patent Assignee: OTSUKA HOLDINGS CO LTD - JP2018/123072, 2018, A Location in patent: Paragraph 0112

76
[ 1102466-62-5 ]
[ 14062-18-1 ]
2-(4-methoxybenzyl)-9-butyl-1H-purin-6(9H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69.7%	With sodium hydride In 1,4-dioxane at 30℃; for 24h; Inert atmosphere;	Synthesis of compound6 General procedure: 55%NaH(3.29 g, 75.5mmol) was added to dried 1,4-dioxane (20 mL). After vigorously stirring at 30°C under N2protection, compound 5 and substituted phenyl ethyl acetates (25.2mmol)were added slowly for 24 hours. After reaction, ethanol was dropped slowly in the mixture until no bubbles are produced. The crude mixture was evaporated invacuo. The residue was stirred vigorously in a biphasic mixture of water (200 mL) andEtOAc(300 mL) at 60°C for 0.5 hour. After cooling to room temperature, the organic phase was dried over MgSO4and concentrated invacuo. Finally, the residual solid was recrystallized fromEtOActo afford the target compound6.

Reference： [1]Huang, Xian-Feng; Cao, Yi-Jing; Zhen, Jing; Zhang, Da-Wei; Kong, Ren; Jiang, Wen-Tao; Xu, Ying; Song, Guo-Qiang; Ke, Heng-Ming; Liu, Li [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 3, p. 481 - 486]

77
[ 14062-18-1 ]
C₁₂H₂₂N₄O [ No CAS ]
2-(4-methoxybenzyl)-9-(2-ethylhexyl)-1H-purin-6(9H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75.2%	With sodium hydride In 1,4-dioxane at 30℃; for 24h; Inert atmosphere;	Synthesis of compound6 General procedure: 55%NaH(3.29 g, 75.5mmol) was added to dried 1,4-dioxane (20 mL). After vigorously stirring at 30°C under N2protection, compound 5 and substituted phenyl ethyl acetates (25.2mmol)were added slowly for 24 hours. After reaction, ethanol was dropped slowly in the mixture until no bubbles are produced. The crude mixture was evaporated invacuo. The residue was stirred vigorously in a biphasic mixture of water (200 mL) andEtOAc(300 mL) at 60°C for 0.5 hour. After cooling to room temperature, the organic phase was dried over MgSO4and concentrated invacuo. Finally, the residual solid was recrystallized fromEtOActo afford the target compound6.

Reference： [1]Huang, Xian-Feng; Cao, Yi-Jing; Zhen, Jing; Zhang, Da-Wei; Kong, Ren; Jiang, Wen-Tao; Xu, Ying; Song, Guo-Qiang; Ke, Heng-Ming; Liu, Li [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 3, p. 481 - 486]

78
[ 14062-18-1 ]
C₁₀H₁₆N₄ [ No CAS ]
2-(4-methoxybenzyl)-9-hexyl-1H-purin-6(9H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77.3%	With sodium hydride In 1,4-dioxane at 30℃; for 24h; Inert atmosphere;	Synthesis of compound6 General procedure: 55%NaH(3.29 g, 75.5mmol) was added to dried 1,4-dioxane (20 mL). After vigorously stirring at 30°C under N2protection, compound 5 and substituted phenyl ethyl acetates (25.2mmol)were added slowly for 24 hours. After reaction, ethanol was dropped slowly in the mixture until no bubbles are produced. The crude mixture was evaporated invacuo. The residue was stirred vigorously in a biphasic mixture of water (200 mL) andEtOAc(300 mL) at 60°C for 0.5 hour. After cooling to room temperature, the organic phase was dried over MgSO4and concentrated invacuo. Finally, the residual solid was recrystallized fromEtOActo afford the target compound6.

Reference： [1]Huang, Xian-Feng; Cao, Yi-Jing; Zhen, Jing; Zhang, Da-Wei; Kong, Ren; Jiang, Wen-Tao; Xu, Ying; Song, Guo-Qiang; Ke, Heng-Ming; Liu, Li [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 3, p. 481 - 486]

79
[ 14062-18-1 ]
C₉H₉Br₂NO₂ [ No CAS ]
(trans)-ethyl 3-(3,5-dibromo-4-methoxyphenylamino)-2-(4-methoxyphenyl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: C₉H₉Br₂NO₂ With sodium methylate In methanol at 20℃; Stage #2: ethyl p-methoxyphenylacetate In methanol	1.3-3.3 (3) Dissolving (cis)-N-3,5-dibromo-4-methoxyphenylcarboximide in 20 equivalents of anhydrous MeOH at room temperature;To the above mixture, 1 equivalent of NaOMe (sodium methoxide) was added.Stir for 15-45 minutes; add 1 equivalent of ethyl 2-(4-methoxyphenyl)acetate and stir for 4-10 hours; after removing excess MeOH, add equal volume of water and stir for 10-20 minutes. The resulting mixture was filtered under reduced pressure to give a white powder.

Reference： [1]Current Patent Assignee: GUANGZHOU UNIVERSITY - CN108685921, 2018, A Location in patent: Paragraph 0061; 0065; 0069; 0074; 0081

80
[ 14062-18-1 ]
5-chloro-3-((4-(difluoromethoxy)phenyl)amino)pyrazine-2-carbaldehyde [ No CAS ]
3-chloro-5-(4-(difluoromethoxy)phenyl)-7-(4-methoxyphenyl)pyrido[2,3-b]pyrazin-6(5H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
17%	With sodium hydroxide In <i>tert</i>-butyl alcohol at 80℃; for 3h;	237.A Step A: 3-chloro-5-(4-(difluoromethoxy)phenyl)-7-(4- methoxyphenyl)pyrido[2,3-b]pyrazin-6(5H)-one To a solution of 5-chloro-3-((4- (difluoromethoxy)phenyl)amino)pyrazine-2-carbaldehyde (120 mg, 0.4 mmol, 1.0 eq.) (synthesized from 3,5-dichloropyrazine-2-carboxylic acid and 4- (difluoromethoxy)aniline via General Procedure VI (Steps A - C)) and ethyl 2-(4- methoxyphenyl)acetate (86 mg, 0.44 mmol, 1.1 eq.) in t-BuOH (5 mL) was added NaOH (32 mg, 0.8 mmol, 2.0 eq.), the reaction mixture was stirred at 80 °C for 3 hrs. the reaction mixture was diluted with H2O (20 ml) and extracted with EtOAc (20 mL x 3), the combined organic layers were washed with brine (10 ml), dried over Na2SO4 and concentrated under reduced pressure, the residue was purified by flash column chromatography on silica gel to afford 3-chloro-5-(4- (difluoromethoxy)phenyl)-7-(4-methoxyphenyl)pyrido[2,3-b]pyrazin-6(5H)-one (30 mg, 17% yield) as a brown solid. LC-MS (ESI) : m/z 430 [M+H]+.

Reference： [1]Current Patent Assignee: AGIOS PHARMACEUTICALS INC; SERVIER MONDE - WO2020/243376, 2020, A1 Location in patent: Paragraph 00452-00454

81
potassium (4-methoxybenzyl)trifluoroborate [ No CAS ]
2-(ethoxycarbonyl)-1,3-dimethyl-1H-imidazole-3-ium trifluoromethanesulfonate [ No CAS ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
19%	With [4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine-N1,N1′]bis{3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-κN]phenyl-κC}iridium(III) hexafluorophosphate In dichloromethane for 18h; Irradiation; Inert atmosphere; Glovebox; Sealed tube;	4.5. General procedure for the esterification of potassiumtrifluoroborate salts General procedure: To an oven-dried 2-dram vial equipped with a stir barwas added the corresponding trifluoroborate salt 3 (0.3 mmol) and the corresponding dimethylimidazolium ester 1 (0.2 mmol). The vial was cycled into the glovebox, and PC1 (0.2 mmol) was added. Dichloromethane (6 mL) was added, and the vial was sealed. Parafilm was wrapped around the cap, and the mixture was irradiated with stirring using four 427 nm Kessil PR160L lamps (~5 cm away). After 18 h, the irradiation was stopped and the reaction mixture was diluted with water (10 mL). The layers were separated and the aqueous layer was extracted with dichloromethane (2x10 mL). The organic layers were combined, dried with sodium sulfate, and concentrated. The unpurified residue was purified using silica gel chromatography (ethyl acetate/hexanes) to afford ester.

Reference： [1]Scheidt, Karl A.; Zhu, Joshua L. [Tetrahedron, 2021, vol. 92]

82
[ 14062-18-1 ]
[ 42201-84-3 ]
[ 32711-91-4 ]

Yield	Reaction Conditions	Operation in experiment
74%	With (tert-Butyldimethylsilyl)bistriflimide In dichloromethane at 20℃; for 12h;

Reference： [1]Han, Zhengyu; Huang, Hai; Meng, Fuliang; Yang, Zhenkun; Zhang, Tianyu; Zhou, Dapeng [Organic and Biomolecular Chemistry, 2021, vol. 19, # 42, p. 9163 - 9166]

83
[ 14062-25-0 ]
[ 38050-71-4 ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
79%	With N<SUP>1</SUP>-(4-hydroxy-2,6-dimethylphenyl)-N<SUP>2</SUP>-(4-hydroxy-3,5-dimethylphenyl)oxalamide; caesium carbonate; copper(I) bromide In 1-methyl-pyrrolidin-2-one; hexane at 80℃; for 12h; Inert atmosphere; Schlenk technique; Sealed tube;

Reference： [1]Li, Chen; Song, Zhi-Qiang; Wang, Dong-Hui; Wang, Jing-Ru [Organic Letters, 2021, vol. 23, # 21, p. 8450 - 8454]

84
[ 14062-18-1 ]
[ 21045-10-3 ]
[ 929687-98-9 ]

Yield	Reaction Conditions	Operation in experiment
60%	Stage #1: ethyl p-methoxyphenylacetate With lithium diisopropyl amide In tetrahydrofuran; hexane; ethylbenzene at -78℃; for 0.916667h; Inert atmosphere; Stage #2: (Z)-5-benzylidene-1,3-dioxolan-2,4-dione In tetrahydrofuran; hexane; ethylbenzene at -78 - 20℃; for 1.66667h; Inert atmosphere;	General procedure for the synthesis of (Z)-5-aryliden-4-hydroxy-3-arylfuran-2(5H)-one (19-24) General procedure: A solution of the appropriate aryl acetate 17 and 18 (3 mmol) in THF (2 mL) was added dropwise via a syringe over a period of 10 min to a solution of lithium diisopropylamide (LDA) 2.0 M solution in THF/ hexane/ethylbenzene (3 mmol, 1.5 mL) in THF (7.5 mL) at -78 °C under nitrogen. The mixture was stirred for 45 min, then the appropriate 1,3-dioxolane-2,4-dione 14-16 (1.0 mmol) in THF (2 mL) was added dropwise over 10 min. The reaction mixture was stirred for 30 min at -78 °C and an additional hour to room temperature, quenched with water (5 mL), and the THF evaporated in vacuum. The resulting aqueous layer was then washed with Et2O (15 mL) and acidified with HCl 10% to pH 1 - 2 in an ice-water bath, to give the corresponding compounds 19-24 as solid products, washed with diethylether and were dried in high vacuum over P2O5.

Reference： [1]Prousis, Kyriakos C.; Katsamakas, Sotirios; Markopoulos, John; Igglessi-Markopoulou, Olga [Synthetic Communications, 2022, vol. 52, # 1, p. 117 - 128]

85
[ 14062-18-1 ]
(Z)-5-(4-chlorobenzylidene)-1,3-dioxolane-2,4-dione [ No CAS ]
(Z)-3-(4-methoxyphenyl)-4-hydroxy-5-(4-chlorobenzylidene)furan-2(5H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	Stage #1: ethyl p-methoxyphenylacetate With lithium diisopropyl amide In tetrahydrofuran; hexane; ethylbenzene at -78℃; for 0.916667h; Inert atmosphere; Stage #2: (Z)-5-(4-chlorobenzylidene)-1,3-dioxolane-2,4-dione In tetrahydrofuran; hexane; ethylbenzene at -78 - 20℃; for 1.66667h; Inert atmosphere;	General procedure for the synthesis of (Z)-5-aryliden-4-hydroxy-3-arylfuran-2(5H)-one (19-24) General procedure: A solution of the appropriate aryl acetate 17 and 18 (3 mmol) in THF (2 mL) was added dropwise via a syringe over a period of 10 min to a solution of lithium diisopropylamide (LDA) 2.0 M solution in THF/ hexane/ethylbenzene (3 mmol, 1.5 mL) in THF (7.5 mL) at -78 °C under nitrogen. The mixture was stirred for 45 min, then the appropriate 1,3-dioxolane-2,4-dione 14-16 (1.0 mmol) in THF (2 mL) was added dropwise over 10 min. The reaction mixture was stirred for 30 min at -78 °C and an additional hour to room temperature, quenched with water (5 mL), and the THF evaporated in vacuum. The resulting aqueous layer was then washed with Et2O (15 mL) and acidified with HCl 10% to pH 1 - 2 in an ice-water bath, to give the corresponding compounds 19-24 as solid products, washed with diethylether and were dried in high vacuum over P2O5.

Reference： [1]Prousis, Kyriakos C.; Katsamakas, Sotirios; Markopoulos, John; Igglessi-Markopoulou, Olga [Synthetic Communications, 2022, vol. 52, # 1, p. 117 - 128]

86
[ 14062-18-1 ]
(Z)-5-(4-methoxybenzylidene)-1,3-dioxolane-2,4-dione [ No CAS ]
[ 100074-26-8 ]

Yield	Reaction Conditions	Operation in experiment
90%	Stage #1: ethyl p-methoxyphenylacetate With lithium diisopropyl amide In tetrahydrofuran; hexane; ethylbenzene at -78℃; for 0.916667h; Inert atmosphere; Stage #2: (Z)-5-(4-methoxybenzylidene)-1,3-dioxolane-2,4-dione In tetrahydrofuran; hexane; ethylbenzene at -78 - 20℃; for 1.66667h; Inert atmosphere;	General procedure for the synthesis of (Z)-5-aryliden-4-hydroxy-3-arylfuran-2(5H)-one (19-24) General procedure: A solution of the appropriate aryl acetate 17 and 18 (3 mmol) in THF (2 mL) was added dropwise via a syringe over a period of 10 min to a solution of lithium diisopropylamide (LDA) 2.0 M solution in THF/ hexane/ethylbenzene (3 mmol, 1.5 mL) in THF (7.5 mL) at -78 °C under nitrogen. The mixture was stirred for 45 min, then the appropriate 1,3-dioxolane-2,4-dione 14-16 (1.0 mmol) in THF (2 mL) was added dropwise over 10 min. The reaction mixture was stirred for 30 min at -78 °C and an additional hour to room temperature, quenched with water (5 mL), and the THF evaporated in vacuum. The resulting aqueous layer was then washed with Et2O (15 mL) and acidified with HCl 10% to pH 1 - 2 in an ice-water bath, to give the corresponding compounds 19-24 as solid products, washed with diethylether and were dried in high vacuum over P2O5.

Reference： [1]Prousis, Kyriakos C.; Katsamakas, Sotirios; Markopoulos, John; Igglessi-Markopoulou, Olga [Synthetic Communications, 2022, vol. 52, # 1, p. 117 - 128]

87
[ 524-38-9 ]
[ 14062-18-1 ]
C₁₉H₁₇NO₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With 2,6-dimethylpyridine; tetrabutylammonium perchlorate In acetone; acetonitrile at 20℃; Inert atmosphere; Electrochemical reaction;	2.1. Procedures for synthesis of products 2 a-n General procedure: A 20 mL two-necked round-bottomed flask was charged with the substrate (0.50 mmol), NHPI (1.0 mmol), 2,6-lutidine (1.5 mmol) and n-Bu 4 NClO 4 (1 mmol). The flask was then equipped with a condenser, a carbon paper (1.0 cm x 1.0 cm) an- ode and a platinum net (1.0 cm x 1.0 cm) cathode, and flushed with nitrogen. Acetonitrile (5.0 mL) and acetone (5.0 mL) were then added. The electrolysis was carried out at room temperature using a constant current of 10 mA until cell voltage at 3.0 V. The residue was chromatographed through silica gel eluting with ethyl acetate/petroleum ether (20:1) to give the desired product.

Reference： [1]Xu, Leitao; Yi, Yangjie; Hu, Sideng; Ye, Jiao; Hu, Aixi [Electrochimica Acta, 2022, vol. 403]

88
[ 14062-25-0 ]
B-methoxy-9-BBN [ No CAS ]
[ 14062-18-1 ]

Yield	Reaction Conditions	Operation in experiment
77%	With N<SUP>1</SUP>-(4-hydroxy-2,6-dimethylphenyl)-N<SUP>2</SUP>-(4-hydroxy-3,5-dimethylphenyl)oxalamide; caesium carbonate In 1-methyl-pyrrolidin-2-one at 80℃; for 12h; Inert atmosphere;	9 The method for methoxylation reaction of aryl or heteroaryl of the present invention specifically includes: Mix 0.2mmol substrate, 0.3mmol coupling agent, 0.01mmol ligand, 1mL solvent, 0.01mmol catalyst and 0.4mmol base in an argon atmosphere and react at 80 for 12h to obtain 30mg 4-methoxyphenyl Ethyl acetate yellow liquid; the yield of 4-methoxyphenyl ethyl acetate is 77%; The structural formula of the substrate is that the coupling agent is MeO-9-BBN; the solvent is N-methylpyrrolidone; the catalyst is cuprous halide; the base is cesium carbonate; the ligand is L3

Reference： [1]Current Patent Assignee: WUYI UNIVERSITY - CN113666826, 2021, A Location in patent: Paragraph 0113-0119

Type	HazMat fee for 500 gram (Estimated)
Excepted Quantity	USD 0.00
Limited Quantity	USD 15-60
Inaccessible (Haz class 6.1), Domestic	USD 80+
Inaccessible (Haz class 6.1), International	USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 100+
Accessible (Haz class 3, 4, 5 or 8), International	USD 200+

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	14062-18-1	MDL No. :	MFCD00040760
Formula :	C₁₁H₁₄O₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	DOCCDOCIYYDLGJ-UHFFFAOYSA-N
M.W :	194.23	Pubchem ID :	84174
Synonyms :

Num. heavy atoms :	14
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.36
Num. rotatable bonds :	5
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	53.61
TPSA :	35.53 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.89 cm/s

[ CAS No. 14062-18-1 ] {[proInfo.proName]}

Quality Control of [ 14062-18-1 ]

Related Doc. of [ 14062-18-1 ]

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[ 14062-18-1 ] Synthesis Path-Upstream 1~2

[ 14062-18-1 ] Synthesis Path-Downstream 1~88

Related Functional Groups of
[ 14062-18-1 ]

Aryls

Ethers

Esters

Precautionary Statements-General

Prevention

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Log Po/w (iLOGP) :	2.21
Log Po/w (XLOGP3) :	2.25
Log Po/w (WLOGP) :	1.8
Log Po/w (MLOGP) :	1.96
Log Po/w (SILICOS-IT) :	2.43
Consensus Log Po/w :	2.13

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Log S (ESOL) :	-2.45
Solubility :	0.691 mg/ml ; 0.00356 mol/l
Class :	Soluble
Log S (Ali) :	-2.63
Solubility :	0.453 mg/ml ; 0.00233 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.41
Solubility :	0.0749 mg/ml ; 0.000385 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.62

Signal Word:	Danger	Class:	3
Precautionary Statements:	P210-P233-P240-P241+P242+P243-P280-P303+P361+P353-P370+P378-P403+P235-P501	UN#:	1993
Hazard Statements:	H225	Packing Group:	Ⅲ
GHS Pictogram:

Precautionary Statements-General
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P222	Do not allow contact with air.
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P230	Keep wetted
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P232	Protect from moisture.
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P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
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P280	Wear protective gloves/protective clothing/eye protection/face protection.
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P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
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P313	Get medical advice/attention.
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P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
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P332	IF SKIN irritation occurs:
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P337	If eye irritation persists:
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P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
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P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

[ CAS No. 14062-18-1 ] {[proInfo.proName]}

Quality Control of [ 14062-18-1 ]

Related Doc. of [ 14062-18-1 ]

Product Details of [ 14062-18-1 ]

Calculated chemistry of [ 14062-18-1 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 14062-18-1 ]

Application In Synthesis of [ 14062-18-1 ]

[ 14062-18-1 ] Synthesis Path-Upstream 1~2

[ 14062-18-1 ] Synthesis Path-Downstream 1~88

Related Functional Groups of [ 14062-18-1 ]

Aryls

Ethers

Esters

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 14062-18-1 ]