Name: 34957-73-8|Methyl 9-hydroxynonanoate|95%
Brand: Ambeed
SKU: A128201
Rating: 93 (29 reviews)

1
[ 67-56-1 ]
[ 3788-56-5 ]
[ 34957-73-8 ]

Yield	Reaction Conditions	Operation in experiment
46%	With sulfuric acid; for 5.0h;Reflux;	To a solution of <strong>[3788-56-5]9-hydroxynonanoic acid</strong> (2) (1.0 g, 5.74 mmol, 1.0 eq) in methanol (30 mL) was added sulfuric acid (1 mL). The reaction mixture was heated to reflux for 5 h. Then the mixture was concentrated under reduced pressure and the residue was diluted with water (15 mL) and ethyl acetate (10 mL). The aqueous layer was back-extracted with additional ethyl acetate (2 x 10 mL). The combined organic layers were washed with brine and dried over anhydrous Na2SC>4. The solvent was removed under reduced pressure and the crude was purified by column chromatography (PE/EA (petroleum ether/ethyl acetate) = 10: 1) to give methyl 9-hydroxynonanoate (3) (500 mg, 46%).

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 5478 - 5480
[2]Bulletin of the Academy of Sciences of the USSR Division of Chemical Science,1984,vol. 33,p. 2574 - 2575
Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya,1984,p. 2809 - 2810
[3]Patent: WO2017/106803,2017,A1 .Location in patent: Page/Page column 0133; 0134
[4]Helvetica Chimica Acta,1929,vol. 12,p. 478
[5]Journal of Organic Chemistry,2010,vol. 75,p. 5334 - 5336

2
[ 34957-73-8 ]
[ 3788-56-5 ]

Reference： [1]Journal of the American Chemical Society,1929,vol. 51,p. 627

3
[ 34957-73-8 ]
[ 1931-63-1 ]

Yield	Reaction Conditions	Operation in experiment
99%	With Celite; pyridinium chlorochromate In dichloromethane at 20℃; for 3.5h;
90%	With Dess-Martin periodane In dichloromethane at 0℃;	2 To a solution of methyl 9-hydroxy nonanoate (1g) in dichloromethane (8ml) at 0°C was added Dess- Martin periodinane (1.7 equiv; 3.83g). The ice bath was removed after 10 minutes, and the reaction was allowed to proceed for up to 2 hours (until no starting material remained by TLC). The reaction was diluted with 200ml of 10% ethyl acetate/hexane, and it was immediately poured onto silica gel. Elution with the same solvent produced the product aldehyde in 90% yield (890mg).
87%	With pyridinium chlorochromate In dichloromethane at 20℃; for 3h; Inert atmosphere; Molecular sieve;

83%	With Celite; pyridinium chlorochromate In dichloromethane at 20℃; for 4h;
81%	With 4 A molecular sieve; pyridinium chlorochromate In dichloromethane at 25℃; for 2.5h;
81%	With dipyridinium dichromate; Celite In dichloromethane at 20℃; for 4h;
80%	With Celite; pyridinium chlorochromate In dichloromethane at 24 - 26℃; for 2h;
71%	With pyridinium chlorochromate In dichloromethane
61%	With pyridinium chlorochromate In dichloromethane
60%	With pyridinium chlorochromate In dichloromethane for 4h; Inert atmosphere;
	With pyridinium chlorochromate In dichloromethane
	With Celite; pyridinium chlorochromate In dichloromethane for 2h; Yield given;
	With oxalyl dichloride; dimethyl sulfoxide; triethylamine 1.) CH₂Cl₂, -78 deg C, 2 h, 2.) CH₂Cl₂, -78 deg C to room temp.; Yield given. Multistep reaction;
	With oxalyl dichloride; dimethyl sulfoxide; triethylamine
	With pyridinium chlorochromate In dichloromethane at 20℃; for 15h;	11.2 Step 2; 9-Oxo-nonanoic acid methyl ester; To a solution of 5.2 g (28 mmol) 9-Hydroxy-nonanoic acid methyl ester in 350 mL DCM is added 9.1 g (41 mmol) Pyridinium chlorochromate and the reaction is stirred for 15 h at rt. The reaction is diluted with DCM, silica is added, the mixture is filtered through a pad of Hyflo and thoroughly washed with DCM. The solvent is removed in vacuo to give the title compound as a green oil, which is used without further purification. MS (method D): 204 [M+H2O]
35.3 g	With manganese(IV) oxide In ethyl acetate at 50℃; for 8h;	1-6 Preparation of methyl 9-oxononanoate Methyl 9-hydroxydecanoate (37.6 g, 0.2 mol) and MnO2 (17.4 g, 0.2 mol) were placed in a reaction kettle, 200 ml of ethyl acetate was added, stirring was started, 180 rpm, temperature 50 ° C, real-time monitoring The reaction was carried out, and after 8 h, it was cooled to room temperature, filtered, and the solvent was evaporated under reduced pressure to give 35.3 g of white solid product
	With sodium hydrogencarbonate; Dess-Martin periodane In dichloromethane at 20℃; for 1h; Inert atmosphere;	Synthesis of compound 2: methyl dec-9-ynoate Methyl 9-hydroxynonanoate (10, 4.00 mmol, 0.753 g) was dissolved in CH2Cl2 (16 mL) and added NaHCO3 (8.00 mmol, 0.672 g, 2.00 equiv.) and Dess-Martin periodinane (4.80 mmol, 2.21 g, 1.30 equiv.). The mixture was stirred at room temperature for one hour under argon, and was then diluted with heptane (80 mL). The resulting mixture was filtered and the filtrate was then passed through a pad of silica gel (3 cm). The silica pad was rinsed with solvent (EtOAc:heptane, 1:4, 200 mL) and the filtrate evaporated in vacuo. The residue was dissolved in dry methanol (40.0 mL). K2CO3 (8.0 mmol, 1.10 g) was added and the system was flushed with argon before dimethyl(1-diazo-2-oxo propyl) phosphonate (4.40 mmol, 1.1 equiv., 10.0 mL 10% in MeCN) was added. After stirring for two hours at room temperature, the mixture was diluted with Et2O (100 mL) and transferred to a separatory funnel. A solution of 5% aq. NaHCO3 (50 mL) was added and the layers were separated. The aqueous layer was extracted with Et2O (1x30 mL) and the organic extracts were combined and washed successively with 5% aq. NaHCO3 (3x30 mL), brine (1x30 mL), dried (MgSO4) and evaporated. The residue was purified by flash chromatography on silica gel (3-5% EtOAc in heptane) to afford the desired product 2 as a colorless oil in 57% yield (0.413 g) from 10. Rf=0.30 (EtOAc:heptane, 1:9. KMnO4-stain). 1H NMR (400 MHz, CDCl3) δ 3.62 (s, 3H), 2.26 (t, J = 7.5 Hz, 2H), 2.14 (td, J = 7.0, 2.6 Hz, 2H), 1.90 (t, J = 2.7 Hz, 1H), 1.65 - 1.53 (m, 2H), 1.53 - 1.43 (m, 2H), 1.32 (m, 6H). 13C NMR (101 MHz, CDCl3) δ 174.2, 84.6, 68.2, 51.5, 34.1, 29.0, 28.8, 28.6, 28.4, 24.9, 18.4. The spectroscopic data was in agreement with that reported in the literature
	With pyridinium chlorochromate In dichloromethane at 20℃; for 1.41667h; Inert atmosphere; Cooling;	Preparation of 10 (methyl-9-oxo-nonanoate) 9(600 μl, 2.8 mmol) was added to a solution of PCC (900 mg, 4.2 mmol) in dry DCM (50 ml) under argon at -15° C., and the mixture was stirred for 45 min. Reaction progress was monitored by TLC. The reaction mixture was allowed to return to room temperature and was stirred for an additional 40 min. The mixture was then filtered over Celite, and the residue was washed with ether. The filtrate was concentrated in vacuo. Flash column chromatography on silica using a gradient of 0-100% ethyl acetate in hexanes afforded 10 at 70% purity (containing about 30% starting material) (305 mg, 1.64 mmol, 58% yield). 1H NMR (600 MHz, chloroform-d): δ (p.p.m.) 9.76 (t, 1.79 Hz, 1H), 3.66 (s, 3H), 2.42 (td, 7.30, 1.77 Hz, 2H), 2.30 (t, 7.60 Hz, 2H), 1.62 (m, 4H), 1.32 (m, 6H).

Reference： [1]Gung, Benjamin W.; Dickson, Hamilton [Organic Letters, 2002, vol. 4, # 15, p. 2517 - 2519]
[2]Current Patent Assignee: GOVERNMENT OF THE UNITED STATES - WO2019/10414, 2019, A1 Location in patent: Page/Page column 78
[3]Nilewski, Christian; Chapelain, Camille Le; Wolfrum, Susanne; Carreira, Erick M. [Organic Letters, 2015, vol. 17, # 22, p. 5602 - 5605]
[4]Gorczynski, Michael J.; Huang, Jinming; King, S. Bruce [Organic Letters, 2006, vol. 8, # 11, p. 2305 - 2308]
[5]Kann, Nina; Rein, Tobias; Akermark, Bjoern; Helquist, Paul [Journal of Organic Chemistry, 1990, vol. 55, # 19, p. 5312 - 5323]
[6]Kai, Kenji; Takeuchi, Jun; Kataoka, Taichi; Yokoyama, Mineyuki; Watanabe, Naoharu [Tetrahedron, 2008, vol. 64, # 28, p. 6760 - 6769]
[7]Lin, De; Zhang, Jianye; Sayre, Lawrence M. [Journal of Organic Chemistry, 2007, vol. 72, # 25, p. 9471 - 9480]
[8]Zakharkin, L. I.; Zhigareva, G. G.; Podvisotskaya, L. S. [Bulletin of the Academy of Sciences of the USSR Division of Chemical Science, 1984, vol. 33, # 12, p. 2574 - 2575][Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1984, # 12, p. 2809 - 2810]
[9]Travelli, Cristina; Aprile, Silvio; Rahimian, Reza; Grolla, Ambra A.; Rogati, Federica; Bertolotti, Mattia; Malagnino, Floriana; Di Paola, Rosanna; Impellizzeri, Daniela; Fusco, Roberta; Mercalli, Valentina; Massarotti, Alberto; Stortini, Giorgio; Terrazzino, Salvatore; Del Grosso, Erika; Fakhfouri, Gohar; Troiani, Maria Pia; Alisi, Maria Alessandra; Grosa, Giorgio; Sorba, Giovanni; Canonico, Pier Luigi; Orsomando, Giuseppe; Cuzzocrea, Salvatore; Genazzani, Armando A.; Galli, Ubaldina; Tron, Gian Cesare [Journal of Medicinal Chemistry, 2017, vol. 60, # 5, p. 1768 - 1792]
[10]Dunny, Elizabeth; Evans, Paul [Journal of Organic Chemistry, 2010, vol. 75, # 15, p. 5334 - 5336]
[11]Gerlach,H. et al. [Helvetica Chimica Acta, 1978, vol. 61, p. 1226 - 1231]
[12]Brunow, Goesta; Stick, Robert V.; Syrjaenen, Kaisa; Tilbrook, D. Matthew G.; Williams, Spencer J. [Australian Journal of Chemistry, 1995, vol. 48, # 11, p. 1893 - 1898]
[13]Okuma, Kentaro; Hirabayashi, Syun-ichi; Ono, Masaaki; Shioji, Kosei; Matsuyama, Haruo; Bestmann, Hans J. [Tetrahedron, 1998, vol. 54, # 17, p. 4243 - 4250]
[14]Moriello, Aniello Schiano; Balas, Laurence; Ligresti, Alessia; Cascio, Maria Grazia; Durand, Thierry; Morera, Enrico; Ortar, Giorgio; Di Marzo, Vincenzo [Journal of Medicinal Chemistry, 2006, vol. 49, # 7, p. 2320 - 2332]
[15]Current Patent Assignee: Novartis (w/o Sandoz); NOVARTIS AG - WO2008/101665, 2008, A1 Location in patent: Page/Page column 185
[16]Current Patent Assignee: BEIJING RISUN TECH - CN109593045, 2019, A Location in patent: Paragraph 0040-0043; 0053-0056; 0066-0069; 0079-0082; 0092
[17]Vik, Anders; Hansen, Trond Vidar; Kuda, Ondrej [Tetrahedron Letters, 2019, vol. 60, # 52]
[18]Current Patent Assignee: BOYCE THOMPSON INSTITUTE; SALK INSTITUTE FOR BIOLOGICAL STUDIES; CORNELL UNIVERSITY - US2019/380336, 2019, A1 Location in patent: Paragraph 0021; 0142

4
[ 110-87-2 ]
[ 34957-73-8 ]
[ 75949-34-7 ]

Yield	Reaction Conditions	Operation in experiment
99%	With pyridinium p-toluenesulfonate In dichloromethane at 20℃;
89%	With toluene-4-sulfonic acid In dichloromethane for 4h; Ambient temperature;
75%	With hydrogenchloride for 22h; Ambient temperature;

	With toluene-4-sulfonic acid In diethyl ether for 6h; Ambient temperature;
	With pyridinium p-toluenesulfonate In dichloromethane; water	R.8.2 Synthesis of methyl 9-(2-tetrahydropyranyloxy) nonanoate (66). [Reference Example 8-2] Synthesis of methyl 9-(2-tetrahydropyranyloxy) nonanoate (66). To a solution of methyl 9-hydroxynonate (65) (852 mg, 4.52 mmol) in dichloromethane (35 ml) were added dihydropyran (1.22 ml, 3.0 eq.) and pyridinium p-toluenesulfonate (PPTS, 352 mg, 0.3 eq.), and the mixture was stirred overnight at room temperature. The reaction mixture was mixed with water and extracted 3 times with dichloromethane. The organic layers were combined, washed with saturated aqueous sodium bicarbonate and brine, successively, dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated in vacuo to give objective Compound 66 (1.37 g, quantitative) as colorless oil. 1H-NMR (270MHz, CDCl3): δ = 4.58 (1H, m, H-2 of THP), 3.88 (1H, m), 3.73 (1H, m), 3.67 (3H, s, OMe), 3.51 (1H, m), 3.38 (1H, m), 2.30 (2H, t, J=7.4 Hz, CH2CO), 1.88-1.46 (10H, m), and 1.31 (8H, m).

Reference： [1]Sonnenberger, Stefan; Lange, Stefan; Langner, Andreas; Neubert, Reinhard H.H.; Dobner, Bodo [Journal of labelled compounds and radiopharmaceuticals, 2016, p. 531 - 542]
[2]Gruiec, Regine; Noiret, Nicolas; Patin, Henri [Journal of the American Oil Chemists' Society, 1995, vol. 72, # 9, p. 1083 - 1085]
[3]Beak, Peter; Zeigler, John M. [Journal of Organic Chemistry, 1981, vol. 46, # 3, p. 619 - 624]
[4]Lehmann, Juergen; Tochtermann, Werner [Tetrahedron, 1999, vol. 55, # 9, p. 2639 - 2658]
[5]Current Patent Assignee: SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem); Sumitomo Pharma (in: Sumitomo Chemical) - EP801071, 1997, A1

5
[ 3095-95-2 ]
[ 34957-73-8 ]
[ 89726-75-0 ]

Yield	Reaction Conditions	Operation in experiment
89%	With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0 - 10℃; for 0.5h;
75%	With dmap; dicyclohexyl-carbodiimide

Reference： [1]Keck, Garry E.; Kachensky, David F.; Enholm, Eric J. [Journal of Organic Chemistry, 1985, vol. 50, # 22, p. 4317 - 4325]
[2]McKay, Catherine; Simpson, Thomas J.; Willis, Christine L.; Forrest, Andrew K.; O'Hanlon, Peter J. [Chemical Communications, 2000, # 13, p. 1109 - 1110]

6
[ 51694-22-5 ]
[ 34957-73-8 ]
[ 95259-34-0 ]

Yield	Reaction Conditions	Operation in experiment
79%	With tributylphosphine In tetrahydrofuran for 0.5h; Ambient temperature;
73%	With tributylphosphine In tetrahydrofuran for 0.5h; Ambient temperature;

Reference： [1]Nakatani; Fukunaga; Haraguchi; et al. [Bulletin of the Chemical Society of Japan, 1986, vol. 59, # 11, p. 3535 - 3539]
[2]Nakatani, Munehiro; Yamachika, Takashi; Tanoue, Takao; Hase, Tsunao [Phytochemistry, 1985, vol. 24, # 1, p. 39 - 42]

7
[ 65827-59-0 ]
[ 34957-73-8 ]
[ 79726-91-3 ]

Yield	Reaction Conditions	Operation in experiment
69%	With 2,4,6-trimethyl-pyridine; silver trifluoromethanesulfonate In nitromethane; toluene at -20℃; for 15h;

Reference： [1]Garegg, Per J.; Hultberg, Hans; Norberg, Thomas [Carbohydrate Research, 1981, vol. 96, p. 59 - 64]

8
[ 55287-60-0 ]
[ 34957-73-8 ]
[ 100644-75-5 ]

Yield	Reaction Conditions	Operation in experiment
68%	With calcium sulfate; silver perchlorate; silver carbonate In dichloromethane at 0℃; for 2h;

Reference： [1]Aspinall, Gerald O.; Gurjar, Mukund K. [Carbohydrate Research, 1985, vol. 143, p. 266 - 270]

9
[ 34957-73-8 ]
[ 358-23-6 ]
[ 115946-08-2 ]

Yield	Reaction Conditions	Operation in experiment
90%	With triethylamine In dichloromethane at -10℃; for 1h;
69.1%	With triethylamine In benzene for 0.5h;

Reference： [1]Klotz, Wolfgang; Schmidt, Richard R. [Journal of Carbohydrate Chemistry, 1994, vol. 13, # 8, p. 1093 - 1102]
[2]Sugawara, Tamio; Igarashi, Kikuo [Carbohydrate Research, 1988, vol. 172, p. 195 - 208]

10
[ 34957-73-8 ]
[ 86861-46-3 ]
[ 108167-19-7 ]

Yield	Reaction Conditions	Operation in experiment
73%	With 2,4,6-trimethyl-pyridine; 4 A molecular sieve; silver trifluoromethanesulfonate In dichloromethane for 15h; Ambient temperature;

Reference： [1]Srivastava, Om P.; Hindsgaul, Ole [Journal of Organic Chemistry, 1987, vol. 52, # 13, p. 2869 - 2875]

11
[ 34957-73-8 ]
[ 70056-63-2 ]
[ 140182-86-1 ]

Yield	Reaction Conditions	Operation in experiment
69%	With silver zeolite In dichloromethane 1.) -78 deg C, 2 h 2.) rt, 16 h;

Reference： [1]Srivastava; Hindsgaul [Carbohydrate Research, 1992, vol. 224, p. 83 - 93]

12
[ 34957-73-8 ]
2,3,6,2',3',4',6'-hepta-O-acetyl-α-D-lactosyl trichloroacetimidate [ No CAS ]
[ 90405-12-2 ]

Yield	Reaction Conditions	Operation in experiment
72%	In dichloromethane at -15℃;

Reference： [1]Dean, Barbara; Oguchi, Hisao; Cai, Shaopei; Otsuji, Eigo; Tashiro, Kazuhiro; et al. [Carbohydrate Research, 1993, vol. 245, # 2, p. 175 - 192]

13
[ 34957-73-8 ]
[ 68124-18-5 ]
[ 146687-15-2 ]

Yield	Reaction Conditions	Operation in experiment
60%	With calcium sulfate; trimethylsilyl trifluoromethanesulfonate In dichloromethane at 4 - 20℃;

Reference： [1]Kashem; Wlasichuk; Gregson; Venot [Carbohydrate Research, 1993, vol. 250, # 1, p. 129 - 144]

14
[ 34957-73-8 ]
[ 95451-93-7 ]
8-(Methoxycarbonyl)octyl 3,4,6-tri-O-acetyl-2-azido-2-deoxy-β-D-mannopyranoside [ No CAS ]
[ 114283-89-5 ]

Yield	Reaction Conditions	Operation in experiment
1: 45.2% 2: 42.6%	With silver silicate; 4 A molecular sieve In toluene at 0℃;

Reference： [1]Sugawara; Irie; Iwasawa; Yoshikawa; Okuno; Watanabe; Kato; Shibukawa; Ito [Carbohydrate Research, 1992, vol. 230, # 1, p. 117 - 149]

15
[ 34957-73-8 ]
[ 68681-00-5 ]
[ 109681-57-4 ]

Yield	Reaction Conditions	Operation in experiment
73%	With 4 A molecular sieve; mercury dibromide In nitromethane for 5h;

Reference： [1]Tsui, David S.; Gorin, Philip A. J. [Carbohydrate Research, 1986, vol. 156, p. 1 - 8]

16
[ 34957-73-8 ]
[ 100759-62-4 ]
[ 110122-36-6 ]

Yield	Reaction Conditions	Operation in experiment
81%	With 4 A molecular sieve; mercury(II) cyanide; mercury dibromide In acetonitrile for 15h;

Reference： [1]Srivastava, Om. P.; Hindsgaul, Ole [Carbohydrate Research, 1986, vol. 155, p. 57 - 72]

17
[ 34957-73-8 ]
[ 67878-15-3 ]

Yield	Reaction Conditions	Operation in experiment
96%	With carbon tetrabromide; triphenylphosphine In dichloromethane at 5℃;
91%	With carbon tetrabromide; triphenylphosphine In dichloromethane at 0℃; for 12h;
89%	With pyridine; bromine; triphenylphosphine In dichloromethane at 0℃; for 2h;

88%	With carbon tetrabromide; triphenylphosphine In toluene at 20℃; for 3h;
	With pyridine; bromine; triphenylphosphine In dichloromethane for 0.5h; Ambient temperature; Yield given;

Reference： [1]Matikainen, Jorma; Kaltia, Seppo; Ala-Peijari, Maija; Petit-Gras, Ninna; Harju, Kirsi; Heikkilä, Jaakko; Yksjärvi, Raija; Hase, Tapio [Tetrahedron, 2003, vol. 59, # 4, p. 567 - 573]
[2]Genard, S.; Patin, H. [Bulletin de la Societe Chimique de France, 1991, # 3, p. 397 - 406]
[3]Location in patent: experimental part Jacquot, Cyril; McGinley, Chris M.; Plata, Erik; Holman, Theodore R.; Van Der Donk, Wilfred A. [Organic and Biomolecular Chemistry, 2008, vol. 6, # 22, p. 4242 - 4252]
[4]Suzuki, Kokichi; Susaki, Hiroshi; Okuno, Satoshi; Sugiyama, Yuichi [Journal of Pharmacology and Experimental Therapeutics, 1999, vol. 288, # 1, p. 57 - 64]
[5]Brunow, Goesta; Stick, Robert V.; Syrjaenen, Kaisa; Tilbrook, D. Matthew G.; Williams, Spencer J. [Australian Journal of Chemistry, 1995, vol. 48, # 11, p. 1893 - 1898]

18
[ 1931-63-1 ]
[ 34957-73-8 ]

Yield	Reaction Conditions	Operation in experiment
97%	With sodium tetrahydroborate In ethanol for 0.25h;
93%	With 5%-palladium/activated carbon; hydrogen In methanol at 50℃; for 4h; Inert atmosphere;
72%	With sodium tetrahydroborate In methanol at 20 - 25℃;

Reference： [1]Keck, Garry E.; Kachensky, David F.; Enholm, Eric J. [Journal of Organic Chemistry, 1985, vol. 50, # 22, p. 4317 - 4325]
[2]Louis, Kevin; Vivier, Laurence; Clacens, Jean-Marc; Brandhorst, Markus; Dubois, Jean-Luc; De Oliveira Vigier, Karine; Pouilloux, Yannick [Green Chemistry, 2014, vol. 16, # 1, p. 96 - 101]
[3]Matikainen, Jorma; Kaltia, Seppo; Ala-Peijari, Maija; Petit-Gras, Ninna; Harju, Kirsi; Heikkilä, Jaakko; Yksjärvi, Raija; Hase, Tapio [Tetrahedron, 2003, vol. 59, # 4, p. 567 - 573]

19
[ 2104-19-0 ]
[ 34957-73-8 ]

Yield	Reaction Conditions	Operation in experiment
99%	With borane-THF; In tetrahydrofuran; at -20 - 20℃; for 4h;	[0418] To prepare 4, a solution of nonanedioic acid monomethyl ester (3) (923 mg, 4.6 mmol) in dry THF (3 ml) at -20C was treated with 1 M BH3 in THF (4.6 ml, 4.6 mmol) over 10 minutes. After stirring at room temperature for 4 hours, the reaction was quenched with 0.77 M aqueous K2C03 solution (10 ml) at 0C. The product was extracted with diethyl ether (3 x 20 ml), washed with saturated aqueous NaCl solution, dried over Na2S04, and concentrated in vacuum to afford methyl 9- hydroxynonanoate (4) (Kai K. et al, Tetrahedron 64:6760-69 (2008), which is hereby incorporated by reference in its entirety) (850 mg, 99% yield) as a colorless oil, which was used directly without any further purification. 1H NMR (400 MHz, chloroform-<ii): delta 1.27-1.37 (8H, m), 1.50-1.66 (4H, m), 2.29 (2H, t, J = 7.5 Hz), 3.62 (2H, t, J 3.66 (3H, s). See Figure 75 C.
55%	With dimethylsulfide borane complex; In tetrahydrofuran; at -20 - 20℃; for 0.333333h;	Preparation of 9-Hydroxy-nonanoic acid methylester 4-BTo a solution of nonanedioic acid monomethyl ester (4.80 g,20 mmol) in THF (20 mE) at -20 C. was added a solution ofborane-dimethylsulfide in THF (2.0 M, 10 mE) over 10 mm.The resulting mixture was stirred for an additional 10 mm,and then allowed to stir at room temperature overnight. Aqueous K2C03 solution was added, and the product was extractedwith ethyl ether (3x). The crude product was purified by flashcolunm chromatography (hexane/EtOAc:2/1) to yield 9-hy-droxy-nonanoic acid methyl ester 4-B (2.0 g, 55%).iH NMR (CDC13) oe 4.86 (bs, 1H, OH), 3.67 (s, 3H), 3.63(t, J=7.4 Hz, 2H), 2.29 (t, J=7.4 Hz, 2H), 1.68-1.48 (m, 4H),1.40-1.24 (m, 8H).
	With potassium carbonate; In tetrahydrofuran; diethyl ether; water;	EXAMPLE 41 4-Hydroxy-3-[10-(4-chlorophenyl)-1-oxodecyl]-2(5H)-furanone To a solution of 165 mL (165 mmol) of a 1.0M solution of boranetetrahydrofuran complex in tetrahydrofuran in 200 mL of dry diethyl ether at 0 C. is added dropwise 25.0 g (123 mmol) of <strong>[2104-19-0]azelaic acid monomethyl ester</strong>, added at such a rate as to prevent excessive release of gas and exothermicity. The solution is allowed to warm to room temperature overnight and is worked up by slowly adding water until gas evolution ceases. Then solid potassium carbonate is added and the organic layer is separated. The aqueous layer is extracted three times with diethyl ether. The combined extracts are washed with brine, dried over Na2 SO4, filtered, and concentrated in vacuo to give 8-carbomethoxyoctan-1-ol as a colorless oil.

	With thionyl chloride;	[Reference Example 8-1] Synthesis of methyl 9-hydroxynonanoate (65). To commercially available <strong>[2104-19-0]azelaic acid monomethyl ester</strong> (2.02 g, 10 mmol) was added thionyl chloride (2.0 ml), and the mixture was refluxed for 5 hours under nitrogen atmosphere. The reaction mixture was cooled to room temperature, and excess thionyl chloride was evaporated to give a residue containing acid chloride 64 . This residue was dissolved in ether (10 ml) and added dropwise into a suspension of sodium borohydride-alumina complex (5.0 g) in ether (15 ml). After stirring for 12 hours at room temperature, the reaction mixture was filtered and was washed with ether. The filtrate was concentrated and resulting residue was purified by column chromatography over silica gel to give objective Compound 65 (1.59 g, Yield: 90%) as colorless oil. [see, Synthesis, 1978 : 891]. 1H-NMR (270MHz, CDCl3): delta = 3.67 (3H, s, CO2Me), 3.62 (2H, t, J=6.6 Hz, CH 2OH), 2.31 (2H, t, J=7.4 Hz, CH 2CO), 2.22 (1H, br.s, OH), 1.70-1.50 (4H, m, CH2x 2), and 1.31 (8H, m).
	With hydrogenchloride; In tetrahydrofuran; diethyl ether;	Step A. Methyl 9-hydroxynonanoate A solution of 9-methoxy-9-oxononanoic acid (<strong>[2104-19-0]azelaic acid monomethyl ester</strong>) (40.45 g, 200 mmol) in tetrahydrofuran (200 mL) was treated via syringe with borane-methyl sulfide complex, 10.0 M (20 mL, 200 mmol) and warmed to 40 C. The reaction was stirred for one hour at ambient temperature. The excess borane reagent was destroyed with excess methanol and the solvent evaporated in vacuo to a residue. The residue was dissolved in diethyl ether and extracted sequentially with 2N hydrochloric acid and water. The organic phase was dried over anhydrous sodium sulfate, filtered through a short pad of silica gel, and the solvent evaporated in vacuo to yield the title compound (33.88 g, 180 mmol) as a viscous oil, which was used without further purification. 1H NMR (DMSO-d6, 300 MHz) delta 4.32 (t, J=5.2 Hz, 1H), 3.58 (s, 3H), 3.37 (td, J=6.7, 5.2 Hz, 2H), 2.48 (t, J=7.4 Hz, 2H), 1.58 (p, J=7.1 Hz, 2H), 1.40 (p, J=7.1 Hz, 2H), 1.26 (broad s, 8H)
		Preparation of 9-{2-[((lR,2S)-l-[(2S,4R)-4-(7-Methoxy-2-phenyl-quinolin-4-yloxy)- pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarbonyl)-sulfamoyl]- phenylaminoj-nonanoic acid; Step l; 9-Hydroxy-nonanoic acid methyl ester; To an ice-cold solution of 10.0 g (45 mmol) Mono-methyl azelate in 250 mL THF is added 90 mL (90 mmol) BH3*THF-Komplex (IM in THF), the ice-bath is removed and stirring is continued at rt for 90 min. The reaction is quenched by careful addition of Methanol, the main solvent is evaporated, the residue is diluted with water and extracted with EtOAc. The combined organic phase is dried with Na2SO4, filtered, and the solvent is removed in vacuo to give the title compound as a colorless oil, which is used without further purification. MS (method D): 206 [M+H2O]

Reference： [1]Bulletin de la Societe Chimique de France,1991,p. 397 - 406
[2]Tetrahedron,2008,vol. 64,p. 6760 - 6769
[3]Patent: WO2013/22985,2013,A2 .Location in patent: Paragraph 0416; 0418
[4]Journal of Medicinal Chemistry,2017,vol. 60,p. 1768 - 1792
[5]Organic Letters,2006,vol. 8,p. 2305 - 2308
[6]Synthetic Communications,1990,vol. 20,p. 907 - 912
[7]Tetrahedron,1998,vol. 54,p. 4243 - 4250
[8]Organic Letters,2002,vol. 4,p. 2517 - 2519
[9]Organic and Biomolecular Chemistry,2008,vol. 6,p. 4242 - 4252
[10]Organic Letters,2015,vol. 17,p. 5602 - 5605
[11]Organic and Biomolecular Chemistry,2017,vol. 15,p. 8614 - 8626
[12]Journal of Organic Chemistry,2007,vol. 72,p. 9471 - 9480
[13]Journal of labelled compounds and radiopharmaceuticals,2016,p. 531 - 542
[14]Carbohydrate Research,1993,vol. 245,p. 175 - 192
[15]Synthetic Communications,2000,vol. 30,p. 941 - 946
[16]Journal of Organic Chemistry,1990,vol. 55,p. 5312 - 5323
[17]Patent: US8637648,2014,B1 .Location in patent: Page/Page column 30
[18]Patent: WO2005/51920,2005,A2 .Location in patent: Page/Page column 10/22
[19]Australian Journal of Chemistry,1995,vol. 48,p. 1893 - 1898
[20]Synlett,1998,p. 1321 - 1322
[21]Journal of Medicinal Chemistry,2006,vol. 49,p. 2320 - 2332
[22]Journal of Organic Chemistry,2001,vol. 66,p. 4766 - 4770
[23]Australian Journal of Chemistry,1995,vol. 48,p. 1893 - 1898
[24]Journal of the Chemical Society. Perkin transactions I,1980,p. 2470 - 2473
[25]Patent: US5242945,1993,A
[26]Patent: EP801071,1997,A1
[27]Journal of the American Chemical Society,2010,vol. 132,p. 16134 - 16145
[28]Patent: US2016/221993,2016,A1 .Location in patent: Paragraph 0025
[29]Patent: US2002/28832,2002,A1
[30]Patent: WO2017/106803,2017,A1
[31]Patent: WO2008/101665,2008,A1 .Location in patent: Page/Page column 185

20
[ 34957-73-8 ]
[ 15900-37-5 ]
[ 133035-31-1 ]

Yield	Reaction Conditions	Operation in experiment
82%	With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran for 72h; Ambient temperature;

Reference： [1]Meanwell; Rosenfeld; Trehan; Romine; Wright; Brassard; Buchanan; Federici; Fleming; Gamberdella; Zavoico; Seiler [Journal of Medicinal Chemistry, 1992, vol. 35, # 19, p. 3498 - 3512]

21
[ 34957-73-8 ]
[ 18162-48-6 ]
[ 110774-17-9 ]

Yield	Reaction Conditions	Operation in experiment
96%	With 1H-imidazole In dichloromethane at 20℃;	4.4.1 TBS-protected alcohol 11 To a stirred solution of 9-hydroxy nonanoate methyl ester (1.0g, 5.31mmol) in dry dichloromethane (5.3mL) was added imidazole (0.48g, 7.0mmol) and then TBSCl (1.1g, 7.0mmol). The resulting solution was stirred overnight at room temperature. Then, the mixture was quenched with water and extracted with dichloromethane (3×20mL). The organic layer was dried over Na2SO4 and concentrated under vacuum. Purification of the crude material on flash column chromatography, eluting with petroleum ether/diethyl ether 97/3, gave pure 11 (1.539g, 96%) as colourless oil. Compound (11): 1H NMR (CDCl3, 400MHz): δ 3.65 (3H, s, -OCH3), 3.58 (2H, t, J=6.5Hz), 2.29 (2H, t, J=7.7Hz), 1.61 (2H, m), 1.49 (2H, m), 1.29 (8H, m), 0.88 (9H, s), -0.03 (6H, s). 13C NMR (62.89MHz CDCl3): δ 174.3 (C), 63.2 (CH2), 21.4 (CH3), 34.1 (CH2), 32.8 (CH2), 29.2 (CH2), 29.1 (CH2), 26.0 (3 CH3), 25.7 (CH2), 24.9 (CH2), 18.3 (C), -5.3 (2 CH3). ES-MS (m/z): 325 [M+Na]+, 303 [M+H]+.
85%	With 1H-imidazole In N,N-dimethyl-formamide for 24h; Ambient temperature;
	With 1H-imidazole In dichloromethane	3.1 Step 1. A solution of methyl 9-hydroxynonanoate (300 mg, 1.6 mmol), tert- butyldimethylchlorosilane (480 mg, 3.2 mmol), and imidazole (240 mg, 3.5 mmol) in DCM (5 mL) was allowed to stir overnight. Brine was added and the mixture was washed with DCM three times. The combined organic layers were dried over MgSO4, filtered and concentrated. Purification by silica gel column chromatography (0 - 50% EtOAc in hexanes) provided methyl 9-[tert-butyl(dimethyl)silyl]oxynonanoate. 1H NMR (400 MHz, Chloroform-d) δ 3.62 (s, 3H), 3.55 (t, J = 6.6 Hz, 2H), 2.26 (t, J = 7.5 Hz, 2H), 1.61 - 1.53 (m, 2H), 1.49 - 1.39 (m, 2H), 1.34 - 1.18 (m, 8H), 0.85 (s, 9H), -0.00 (s, 6H).

With 1H-imidazole In dichloromethane

3.1 Step 1. A solution of methyl 9-hydroxynonanoate (300 mg, 1.6 mmol), tert- butyldimethylchlorosilane (480 mg, 3.2 mmol), and imidazole (240 mg, 3.5 mmol) in DCM (5 mL) was allowed to stir overnight. Brine was added and the mixture was washed with DCM three times. The combined organic layers were dried over MgSO4, filtered and concentrated. Purification by silica gel column chromatography (0 - 50% EtOAc in hexanes) provided methyl 9-[tert-butyl(dimethyl)silyl]oxynonanoate. 1H NMR (400 MHz, Chloroform-d) δ 3.62 (s, 3H), 3.55 (t, J = 6.6 Hz, 2H), 2.26 (t, J = 7.5 Hz, 2H), 1.61 - 1.53 (m, 2H), 1.49 - 1.39 (m, 2H), 1.34 - 1.18 (m, 8H), 0.85 (s, 9H), -0.00 (s, 6H).

Reference： [1]Fortunati, Tancredi; D'Acunto, Mariantonietta; Caruso, Tonino; Spinella, Aldo [Tetrahedron, 2015, vol. 71, # 16, p. 2357 - 2362]
[2]Kallury, R. Krishnamohanrao; Krull, Ulrich J.; Thompson, Michael [Journal of Organic Chemistry, 1987, vol. 52, # 24, p. 5478 - 5480]
[3]Current Patent Assignee: GILEAD SCIENCES INC - WO2021/222353, 2021, A1 Location in patent: Page/Page column 259; 290
[4]Current Patent Assignee: GILEAD SCIENCES INC - WO2021/222353, 2021, A1 Location in patent: Page/Page column 259; 290

22
[ 34957-73-8 ]
[ 124-63-0 ]
[ 117407-87-1 ]

Yield	Reaction Conditions	Operation in experiment
77%	With triethylamine In dichloromethane at 0℃; for 1h;
68%	With pyridine In dichloromethane at 0 - 20℃; for 24h;	1 Dichloromethane (20 mL) was added with methyl 9-hydroxynonanoate (2.1 g) and pyridine (1.8 g), stirred at 0°C, added with methanesulfonyl chloride (1.3 mL), gradually warmed to room temperature and stirred for one day. The reaction solution was added with water and then extracted twice with dichloromethane. The resulting organic layer was washed with 1 N hydrochloric acid and saturated sodium hydrogencarbonate solution. The organic layer was dried over anhydrous sodium sulfate, and then the solvent was removed. The resulting residue was purified by silica gel column chromatography to obtain methyl 9-(methanesulfonyloxy)nonanoate (2.1 g, yield: 68%).
	With triethylamine In dichloromethane at 0℃; for 0.5h; Yield given;

With pyridine In dichloromethane at 0 - 20℃;

d1-4 Preparation of Compound d1-4 Methyl 9-hydroxynonanoate and pyridine were added to dichloromethane. The solution was stirred at 0°C, added with methanesulfonyl chloride, and further stirred with gradually warming up to room temperature. The solution was added with water, and extracted twice with dichloromethane. The resulting organic layer was washed with 1N hydrochloric acid and saturated sodium hydrogen carbonate. After the organic layer was dried over anhydrous sodium sulfate, the solvent was removed and the residue was purified by silica gel column chromatography to obtain methyl 9- (methane sulfonyloxy)nonanoate.

Reference： [1]Von Delius, Max; Geertsema, Edzard M.; Leigh, David A.; Tang, Dan-Tam D. [Journal of the American Chemical Society, 2010, vol. 132, # 45, p. 16134 - 16145]
[2]Current Patent Assignee: FUJIFILM HOLDINGS CORP. - EP1426353, 2004, A1 Location in patent: Page 14
[3]Klein; Yeung; Kurath; Mao; Fernandes; Lartey; Pernet [Journal of Medicinal Chemistry, 1989, vol. 32, # 1, p. 151 - 160]
[4]Current Patent Assignee: FUJIFILM HOLDINGS CORP. - EP1916255, 2008, A2 Location in patent: Page/Page column 30

23
[ 34957-73-8 ]
[ 3068-34-6 ]
[ 77111-92-3 ]

Yield	Reaction Conditions	Operation in experiment
90%	With mercury(II) cyanide In benzene at 25℃;

Reference： [1]Horton, Derek; Samreth, Soth [Carbohydrate Research, 1982, vol. 103, p. C12 - C23]

24
[ 34957-73-8 ]
[ 3068-34-6 ]
[ 77111-92-3 ]
2-methyl-(3,4,6-tri-O-acetyl-1,2-dideoxy-α-D-glucopyranoso)[1,2-d]-2-oxazoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With tin(II) trifluoromethanesulfonate; 4 A molecular sieve; tetramethylurea In dichloromethane for 48h; Ambient temperature;

Reference： [1]Lubineau, Andre; Gallic, Joelle Le; Malleron, Annie [Tetrahedron Letters, 1987, vol. 28, # 42, p. 5041 - 5044]

25
[ 34957-73-8 ]
[ 13242-53-0 ]
[ 110524-42-0 ]

Yield	Reaction Conditions	Operation in experiment
60%	With 4 A molecular sieve; mercury(II) cyanide; mercury dibromide In acetonitrile for 15h;
57.9%	With calcium sulfate; mercury(II) cyanide In nitromethane for 72h; Ambient temperature;

Reference： [1]Srivastava; Hindsgaul [Carbohydrate research, 1987, vol. 161, # 2, p. 195 - 210]
[2]Wada, Kaoru; Chiba, Taku; Takei, Yutaka; Ishihara, Hideko; Hayashi, Hidetoshi; Onozaki, Kikuo [Journal of Carbohydrate Chemistry, 1994, vol. 13, # 7, p. 941 - 966]

26
[ 34957-73-8 ]
[ 154410-62-5 ]
8-Methoxycarbonyloctyl O-(2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl)-(1->3)-O-<2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl-(1->6)>-2,4-di-O-benzoyl-β-D-glucopyranoside [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With N-iodo-succinimide; 4 A molecular sieve; silver trifluoromethanesulfonate In dichloromethane; toluene at -20℃; for 0.166667h;