* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With palladium on activated charcoal; hydrogen In methanol at 20℃;
[00324j Synthesis of compound 9.3. Into a 2-L 3-necked round-bottom flask, was placed a solution of compound 9.2 (25.6 g, 143.67 mmol, 1.00 equiv) in methanol (1 L) and Pd/C (8 g). Hydrogen gas was introduced and reaction was stirred overnight at room temperature. Solids were filtered out, and solvents removed under reduced pressure to furnish 25.7 g (99percent) of compound 9.3 as a white solid.
Reference:
[1] Applied Organometallic Chemistry, 2011, vol. 25, # 1, p. 1 - 8
[2] Patent: WO2014/182950, 2014, A1, . Location in patent: Paragraph 00322; 00324
[3] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1981, p. 336 - 343
[4] Journal of Organic Chemistry, 1970, vol. 35, p. 647 - 651
2
[ 141-82-2 ]
[ 135-02-4 ]
[ 6099-03-2 ]
Yield
Reaction Conditions
Operation in experiment
98%
With piperidine In pyridine at 85℃;
[00323j Synthesis of compound 9.2. A 500-mL 3-necked round-bottom flask was charged with solution of compound 9.1 (20 g, 146.90 mmol, 1.00 equiv) in pyridine (250 mL), propanedioic acid (18.3 g, 175.86 mmol, 1.20 equiv), and piperidine (2.5 g, 29.36 mmol, 0.20 equiv). Reaction was stirred overnight at 85 °C. Upon completion, solvents were reduced under vacuum and pH value of the solution was adjusted to 3.0 using HC1. Resulting solids were collected by filtration, which provided 25.6 g (98percent) of compound 9.2 as a white solid.
Reference:
[1] Patent: WO2014/182950, 2014, A1, . Location in patent: Paragraph 00322; 00323
[2] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1981, p. 336 - 343
[3] Journal of the Indian Chemical Society, 1988, vol. 65, # 3, p. 187 - 191
[4] Molecules, 2009, vol. 14, # 10, p. 4166 - 4179
[5] Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 15, p. 4513 - 4519
[6] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 1, p. 53 - 56
[7] Molecules, 2014, vol. 19, # 10, p. 16058 - 16081
[8] Chemistry - A European Journal, 2017, vol. 23, # 3, p. 554 - 557
3
[ 64-19-7 ]
[ 135-02-4 ]
[ 6099-03-2 ]
Yield
Reaction Conditions
Operation in experiment
53%
Stage #1: at 10 - 100℃; for 1.5 h; Stage #2: at 185 - 190℃; for 10 h; Reflux
General procedure: Acrylic acids 3a-f were prepared according to Chiriac et al.10 A 500 mL three necked round bottom flask equipped with a reflux condenser carrying calcium chloride guard tube, kept in ice-bath, was charged with acetic acid (0.7 mol). Under stirring, sodium borohydride (0.133 mol) was added slowly in small portions into the flask. During this the temperature was maintained below 10°C. The mixture was stirred for half hour at RT and then for one hour at 90-100°C in an oil bath. To this solution, aldehyde (0.1 mol) was added and then N-methyl pyrrolidone (9.91 g) was added as solvent. This solution was refluxed at 185-90°C for 10 hr in an oil bath. After cooling to RT, the above reaction mixture was treated with 50 mL of water and then with saturated sodium bicarbonate solution with vigorous shaking. There was an alkaline reaction and after completion of the reaction it was filtered. To remove the unreactive aldehyde, the filtrate was distilled under vacuum, until the distillate was no longer cloudy. The solution was treated with hydrochloric acid solution (2.7 N) till there was no further reaction. The precipitates of acid were obtained. Absence of spot of aldehyde on thin layer chromatographic plates revealed the homogeneity of acid.
Reference:
[1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2013, vol. 52, # 12, p. 1513 - 1520
With potassium hydroxide; In ethylene glycol; at 180℃; for 1h;Reflux;
In a dry 100 mL single-necked flask,Followed by the addition of <strong>[6099-03-2]o-methoxycinnamic acid</strong> (compound l, 25 g, 0.14 mol)Potassium oxide (17 g, 0.3 mol) and 60 mL ethylene glycol.The mixture was heated to reflux for 1 hour,Followed by distillation, collecting 140 to 150 C fractions,When the temperature rises to 180 C, stop the distillation.To give 15.6 g of a pale yellow oil,Is o-methoxystyrene (compound 2),Yield 83% AC purity 95%Without purification,Can be used directly for subsequent reactions.
With palladium on activated charcoal; hydrogen; In methanol; at 20℃;
[00324j Synthesis of compound 9.3. Into a 2-L 3-necked round-bottom flask, was placed a solution of compound 9.2 (25.6 g, 143.67 mmol, 1.00 equiv) in methanol (1 L) and Pd/C (8 g). Hydrogen gas was introduced and reaction was stirred overnight at room temperature. Solids were filtered out, and solvents removed under reduced pressure to furnish 25.7 g (99%) of compound 9.3 as a white solid.
With oxalyl dichloride; In dichloromethane; for 3h;
General procedure: Oxalyl chloride (1 ml) was added to the dichloromethane (10 ml) solutions of substituted cinnamic acid (2 mmol). The reaction mixture was stirred until the bubbling stopped (approximately 3 hours), and vaporized in vacuo. The cinnamoyl chloride was used directly without purification.
With thionyl chloride; for 2h;Reflux;
General procedure: Compound 10 was prepared by a procedure similar to that of Lu and co-workers, and Nagao and co-workers. A solution of octanoic acid (4.43g, 30.74mmol) and thionyl chloride (20mL) was heated under reflux for 3h. The excess thionyl chloride was removed in vacuo and the crude octanoyl chloride taken through to the next step without further purification. A solution of 2 (12.0g, 21.55mmol), triethylamine (4.6mL, 33.3mmol), dimethylaminopyridine (0.26g, 2.16mmol) and crude octanoyl chloride in dimethylformamide (150mL) was then stirred at room temperature for 3h. The mixture was then diluted with ethyl acetate (200mL) and washed with water (200mL). The separated aqueous phase was further extracted with ethyl acetate (2×100mL) and the combined organic phases washed with brine (4×100mL), dried over anhydrous magnesium sulfate, filtered and the solvent removed in vacuo. Purification by flash chromatography (hexane/ethyl acetate 2:1) afforded 10 as an off-white solid (9.92g, 14.66mmol, 68%).
With thionyl chloride; at 75℃; for 2h;
General procedure: Compounds A11-A15, A17, A18, A20-A22, B1-B12, C7-C10 and C13-C20 were preparedaccording to method B in Fig 1 by reaction of the corresponding acyl chloride and thecorresponding alcohol. The general procedure was as follows. The mixture of cinnamic acid orcinnamic acids with substituents on the phenyl ring (0.10 mol) and 30 mL thionyl chloridewas refluxed at 75C for 2 h. The excess thionyl chloride was removed under reduced pressure.After the residue was dissolved in 10 mL DCM, the corresponding alcohol (10 mmol) wasadded at 0C. The solution was stirred at 0C for 1 h, and then washed with water (3 × 30 mL)followed by 5% Na2CO3 aqueous solution, and dried over anhydrous sodium sulfate. After filtration,the solvent was removed under reduced pressure. The residue was purified by silica gelcolumn chromatography ( 40 mm × L 40 cm) to afford the desired product.
With thionyl chloride; at 80℃; for 3h;Inert atmosphere;
General procedure: The carboxylic acid (5, 1equiv.) was refluxed with thionyl chloride (120equiv.) and the mixture heated under reflux for 3h. The solution was cooled to room temperature and concentrated under reduced pressure. The residue was further dried via high vacuum and used in the proceeding reaction without further purification. KSCN (1-2equiv.) was added to the solution of crude acyl chloride in anhydrous acetonitrile (0.5M) and the reaction was allowed to stir for 4h at room temperature. The solid KCl was removed through filtration and the aniline (7, 1equiv.), dissolved in acetonitrile (0.1M), was added drop wise to the filtrate and the mixture stirred for 24h.31 The product either precipitated and needed no further purification, recrystallized using the appropriate mixture of solvents or purified via flash column chromatography or preparative HPLC.
With thionyl chloride;Reflux;
General procedure: A mixture of various substituted cinnamic acid (0.01 mol) and thionyl chloride (10.0 ml) was heated under reflux condition and stirred for 4-5 h. The progress of the reaction was monitored by TLC. After the completion of the reaction,the unreacted thionyl chloride was removed under reduced pressure by distillation, and then remaining residue was used for further step without recrystallization. Similarly, other compounds were also prepared.
With oxalyl dichloride; In N,N-dimethyl-formamide; at 0 - 5℃; for 1h;
In a fume hood, add VI91.42 g (0.008 mol) to a 50 mL pear-shaped bottle, add 0.25 mL of N, N-dimethylformamide (DMF) dropwise, and cool to 0-5 C in an ice bath. Slowly add 2.00 mL (0.021 mol) of oxalyl chloride, and the addition is completed within 10 minutes. After dripping, the ice bath was removed, and the reaction was continued for 1 h until the solution was clear, and no gas was generated in the system. Use a rotary evaporator to evaporate the excess solvent and oxalyl chloride to obtain VII9. Add 16 mL of dichloromethane to dissolve it and seal it for later use.
[00323j Synthesis of compound 9.2. A 500-mL 3-necked round-bottom flask was charged with solution of compound 9.1 (20 g, 146.90 mmol, 1.00 equiv) in pyridine (250 mL), propanedioic acid (18.3 g, 175.86 mmol, 1.20 equiv), and piperidine (2.5 g, 29.36 mmol, 0.20 equiv). Reaction was stirred overnight at 85 C. Upon completion, solvents were reduced under vacuum and pH value of the solution was adjusted to 3.0 using HC1. Resulting solids were collected by filtration, which provided 25.6 g (98%) of compound 9.2 as a white solid.
63.21%
With pyridine; ammonium acetate; at 85℃; for 5h;Darkness;
A 50 mL round bottom flask with a reflux condenser was charged with 3.26 g (0.024 mol) of 2-methoxybenzaldehyde, 4.90 g (0.047 mol) of malonic acid, 0.18 g (0.023 mol) of ammonium acetate, and 16 mL of pyridine. Put it on an oil bath and heat to 85 C. Refrigerate at reflux for 5h. The reaction was stopped, left to cool to room temperature, and poured into 50 mL of ice water. The pH was adjusted to about 2 with dilute hydrochloric acid, and a large amount of solid was precipitated. The solid was filtered by suction, and the solid was washed with water until it had no pyridine smell. Dry to obtain a solid product. Recrystallization using anhydrous ethanol to obtain VI9 as a white solid, yield 63.21%, melting point 184.0-184.5 C.
With piperidine; pyridine; at 80 - 90℃; for 24h;
General procedure: A mixture of aromatic aldehydes (3.2 mmol), malonic acid (3.87 mmol), piperidine (0.387 mmol) was dissolved in pyridine and stirred on 80-90 C for 24 h. The pyridine was removed at the vacuum. The reaction mixture was poured in water and washed with HCl, the precipitate was filtered and washed with hexane about three times, and dried under vacuum to afford the cinnamic acids (Scheme 1).
With piperidine; pyridine; for 6h;Reflux;
General procedure: A mixture of benzaldehyde (30 mmol), malonic acid (120 mmol), and piperidine (2 mL) in pyridine was refluxed in a 250 mL single neck round bottomed flask (SNRB) for 6 h. Upon completion, the reaction mixture was poured into a 1 L Erlenmeyer flask (EF) containing cold, dilute HCl (200 mL) and stirred for 10 min. The resulting precipitate was filtered and washed with cold water to afford I.
6,22-Dioxo-2,10,20,24-tetraoxa-tricyclo[26.4.0.011,16]dotriaconta-1(28),11(16),12,14,29,31-hexaene-5,21-dicarboxylic acid 21-ethyl ester 5-methyl ester[ No CAS ]
With N,N-dimethyl-formamide; potassium bromide; trichlorophosphate; In acetonitrile; at 20℃;Sonication;
General procedure: To a centimolar cinnamic acid, 0.015 mol of Vilsmeier-Haackreagent and KBr and solvent (Me CN) were added in a cleanin a round bottom flask and clamped in a sonicator at roomtemperature. After completion of the reaction, as ascertainedby TLC, the reaction mixture is treated with sodium thiosulfate solution, followed by the addition of ethyl acetate. Theseparation and purification procedure is by and large similarto the above procedure.
With triethylamine; In dichloromethane; at 20℃;Cooling with ice;
General procedure: In a three-necked round-bottomed flask containing substituted cinnamic acid (0.05 mol), dichloromethane (50ml) and triethylamine (0.1 mol), methyl chloroformate (0.1 mol) were added slowly, dropwise with cooling in an ice bath, the mixture was stirred 2 h at room temperature. Then, 1,2-ethylenediamine (0.025 mol) was added dropwise slowly, under an ice bath with stirring, and the mixture was stirred 6-8 h at room temperature. The solvents were removed under reduced pressure. The residue was poured into 100 ml ice water and stirred for 10 min. The solid obtained after filtration was purified either by recrystallization in hot methanol or by column purification using flash chromatography (SiO2, 35 % EtOAc/hexanes).
With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 0 - 20℃;
General procedure: A solution of 1 (0.2 mmol), DMAP (0.2 equiv), and the proper cinnamic acid (1.2 equiv) in anhydrous CH2Cl2 (8 mL) was added DCC (1.2 equiv) at 0 C. The resulting mixture was stirred at room temperature until the starting material was not observed by TLC. The reaction mixture was filtered, and the residue was washed with CH2Cl2 (2 × 10 mL). The CH2Cl2 solution was washed with 5% HCl (3 × 30 mL), saturated NaHCO3 (3 × 30 mL) and saturated NaCl (3 × 30 mL), respectively. The organic layer was dried over anhydrous Na2SO4 and concentrated to dryness under reduced pressure. The residue was chromatographed using a silica gel column to yield the pure target compounds.
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 12h;Inert atmosphere;
General procedure: (E)-3-(4-ethylphenyl)acrylic acid (100 mg, 0.567 mmol), 3-((ethylimino)methyleneamino)-N,N-dimethylpropan-1-aminium chloride (163 mg, 0. 851 mmol), and N,N-dimethylpyridin-4-amine (13 mg, 0.19 mmol) were dissolved in dichloromethane (10 mL). N-ethyl-N-isopropylpropan-2-amine (161 mg, 1.248 mmol) was added followed by 4,5-dihydrothiazol-2-amine (64 mg, 0.624 mmol). The reaction mixture was stirred for 12 hours at room temperature. The reaction was concentrated under vacuum. Purification by column chromatography provided (E)-N-(4,5-dihydrothiazol-2-yl)-3-(4-ethylphenyl)acrylamide as a white powder (58 mg, 40% yield).
General procedure: To a solution of compound 5 (1.0 equiv) in CH2Cl2 was added the corresponding 3-aromatic acrylic acid (1.5 equiv), DMAP (1.0 equiv) and EDC (1.5 equiv), and then the mixture was stirred at room temperature for 7 h. The mixture was diluted with CH2Cl2, washed with saturated aqueous NaHCO3 and brine, dried over anhydrous Na2SO4, concentrated under reduced pressure to give the crude product. Purification by column chromatography (CH2Cl2/CH3OH = 20:1) afforded compounds 6-29.
(E)-1-(2-cyclohexylvinyl)-2-methoxybenzene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
85%
With iron(III)-acetylacetonate; di-tert-butyl peroxide; at 120℃; for 24h;Inert atmosphere;
General procedure: To a Schlenk tube equipped witha magnetic stir bar were added Fe(acac)3 (21.2 mg, 0.06 mmol)and cinnamic acid (0.3 mmol) under a nitrogen atmosphere.Cycloalkane (2.0 mL, 15-25 mmol) and DTBP (di-tert-butylperoxide, 0.6 mmol, 113 muL) were added under a nitrogenatmosphere and the resulting reaction mixture was stirred at 120C for 24 h. After cooling to room temperature and removal ofvolatiles, the products were isolated by flash column chromatography(PE)
General procedure: To a solution of 1, 2, 3, 4 and 5 (2.5 eq) in CH2Cl2 (5 mL) were added N,N'-dicyclohexylcarbodiimide (DCC, 2.7 eq) and 4-dimethylaminopyridine (DMAP, catalytic amount). The reaction mixture was stirred at 0 C for 30 min. 10 or 11 (1 eq) in CH2Cl2 was added dropwise at room temperature under N2 gas. The product was filtrated and solvent was removed under reduced pressure. The crude product was subsequently purified by silica gel column to afford bis-acetonides 1R-5R.
General procedure: To a solution of 1, 2, 3, 4 and 5 (2.5 eq) in CH2Cl2 (5 mL) were added N,N'-dicyclohexylcarbodiimide (DCC, 2.7 eq) and 4-dimethylaminopyridine (DMAP, catalytic amount). The reaction mixture was stirred at 0 C for 30 min. 10 or 11 (1 eq) in CH2Cl2 was added dropwise at room temperature under N2 gas. The product was filtrated and solvent was removed under reduced pressure. The crude product was subsequently purified by silica gel column to afford bis-acetonides 1R-5R.