|
With thionyl chloride; |
REFERENCE EXAMPLE 30 2,3-Dimethylbenzoyl chloride As described for Reference Example 26, 3.0 g of <strong>[603-79-2]2,3-<strong>[603-79-2]dimethylbenzoic acid</strong></strong> is reacted with 40 ml of thionyl chloride to give 3.2 g of the product as a colorless oil. |
|
With thionyl chloride; |
Reference Example 25 2,3-Dimethylbenzoyl chloride As described for Reference Example 21, 3.0 g of <strong>[603-79-2]2,3-<strong>[603-79-2]dimethylbenzoic acid</strong></strong> is reacted with 40 ml of thionyl chloride to give 3.2 g of the product as a colorless oil. |
|
With thionyl chloride; at 80℃; for 1h;Product distribution / selectivity; |
A solution of <strong>[603-79-2]2,3-<strong>[603-79-2]dimethylbenzoic acid</strong></strong> (100 g, 666 mmol) in thionyl chloride (350 ml) was heated at 80 C. for 1 h, before cooling to room temperature and concentrating in vacuo. To the residue was added toluene (100 ml) and the solution was again concentrated in vacuo. The intermediate acid chloride was added to a mixture of 1-benzylimidazole (100 g, 632 mmol) and triethylamine (100 ml) in acetonitrile (1 l) and the reaction mixture was heated at reflux for 18 h. The reaction mixture was concentrated in vacuo and to the residue was added diethyl ether (500 ml) and ethyl acetate (50 ml). This solution was washed with water (500 ml) and saturated aqueous sodium hydrogen carbonate solution (500 ml), filtered through silica gel (100 g) and concentrated in vacuo to give the title compound (182 g).Experimental MH+ 291.4; expected 291.1 |
|
With oxalyl dichloride;N,N-dimethyl-formamide; In toluene; at 20℃; for 4h;Product distribution / selectivity; |
To a solution of <strong>[603-79-2]2,3-<strong>[603-79-2]dimethylbenzoic acid</strong></strong> (2.0 kg, 13.2 mol) in toluene (20 L) was added N,N-dimethylformamide (20 ml), followed by oxalyl chloride (2.0 kg, 15.6 mol) at room temperature. The reaction mixture was stirred at room temperature for 4 h and monitored by thin layer chromatography. If necessary, excess oxalyl chloride (25 g) was added until no starting material was observed. Excess toluene and oxalyl chloride were removed by distillation under vacuum at temperatures below 70 C. To the residue was added toluene (150 ml) and the mixture was again concentrated in vacuo to give 2,3-dimethylbenzoyl chloride (2.0 kg).To a solution of 1-benzyl-1H-imidazole (1.69 Kg, 10.56 mol) in dichloromethane (14.0 L), at -7 C., was added triethylamine (1.61 kg, 10.56 mol). A solution of 2,3-dimethylbenzoyl chloride (2.0 kg, 11.99 mol) in dichloromethane (6.0 L) was then added dropwise and the reaction mixture was stirred at room temperature for 16 h. The reaction was monitored by Thin layer Chromatography. After completion of the reaction, the reaction mixture was diluted with water (5.0 L) and the mixture was stirred for a further 15 min. The two layers were separated and the organic phase was concentrated in vacuo. To the residue was added toluene (8.0 L) and the solution was cooled to -5 C., before addition of hydrochloric acid (5N, 8.0 L). The two layers were separated and the aqueous layer was adjusted to pH 9-12, by addition of aqueous sodium hydroxide solution (50%), and extracted with toluene (4.0 L and then 8.0 L). The combined organic phases were concentrated in vacuo to give the title compound (2.8 kg). |
|
With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; at 15 - 25℃; for 2h;Product distribution / selectivity; |
Step-lb: Preparation of (2,3-dimethylphenyl)-imidazol-l-yl-methanone.To the compound 1 (250 g, 1.66 mol) in dry dichloromethane (1.8 L) was added N- dimethylformamide (15 ml) and oxalyl chloride (222 g, 1.75 mol) at about 15 C for about 1 h and continued stirring for about 1 h at about 25 C. A solution of imidazole (225.7 g, 3.32 mol) in dichloromethane (1.8 L) was added dropwise at about 0 C and stirred for about 1 h. The reaction mixture was quenched with ice-cold water (1.5 L) and extracted with dichloromethane. The organic layer was washed with sat. NaHC03 solution (1.25 L), dried over anhydrous sodium sulphate and concentrated under reduced pressure to get 2b as a yellowish syrupy mass. Yield 291 g (87 %)..H NMR (300 MHz, CDC13): delta 7.84 (s, 1H), 7.46- 7.35 (m, 2H), 7.23 (d, J = 4.8 Hz, 2H), 7.1 1 (m, 1H), 2.36 (s, 3H), 2.22 (s, 3H)LCMS (m z): 200.6 (M+l) |
|
With thionyl chloride; at 0℃; for 16h;Reflux; |
SOCl2 (3.0 g, 25 mmol) was added to <strong>[603-79-2]2,3-<strong>[603-79-2]dimethylbenzoic acid</strong></strong> 40 (1.00 g, 6.7 mmol) at 0 C. The mixture was heated at reflux for 16 h. The evaporation residue, in CH2Cl2 (1.0 mL), was added dropwise to Me2NH in water (40%, 3.7 mL) at 0-20 C. The mixture was stirred at 20 C for 1 h, diluted with CH2Cl2, washed (water, 3*) and dried. Evaporation gave 41 (990 mg, 84%) as a pale yellow oil: 1H NMR (CDCl3) (COSY/NOESY) delta 2.16 (3H, s, 2-Me), 2.27 (3H, s, 3-Me), 2.81 (3H, s, N-Me), 3.12 (3H, s, N-Me'), 6.99 (1H, dd, J = 7.2, 1.8 Hz, 4-H), 7.10 (1H, t, J = 7.5 Hz, 5-H), 7.13 (1H, dd, J = 7.6, 1.8 Hz, 6-H); 13C NMR (CDCl3) (HSQC/HMBC) delta 16.00 (2-Me), 20.03 (3-Me), 34.48 (N-Me'), 38.37 (N-Me), 123.40 (4-C), 125.82 (5-C), 130.01 (6-C), 132.25 (2-C), 137.02 (1-C), 137.42 (3-C), 171.99 (C=O); MS m/z 178.1226 (M+H)+ (C11H16NO requires 178.1232). |
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
HazMat Fee +
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
