methyl 5-fluoro-2-(trifluoromethyl)benzoate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 4.48 g (22.5 mmol) 5-Fluoro-2-trifluoromethyl-benzoic acid methyl ester (Rarechem) and 60.0 ml dimethylsulphoxid were added 2.23 g (27.0 mmol) dimethylamine hydrochloride and 6.54 g (47.3 mmol) potassium carbonate. The reaction mixture was stirred for 8 h at 60° C. in an autoclave and was reduced with high vacuum rotation evaporator at 65° C. The residue was diluted with dichloromethane, washed twice with water. The combined water phases were extracted with dichloromethane. The combined dichloromethane phases were washed with diluted sodium hydrogen carbonate solution, dried with sodium sulphate and concentrated. The oily crude was purified by column chromatography and the desired product 15a was obtained in 72% yield (4.00 g, 16.2 mmol). was reduced with high vacuum rotation evaporator at 65° C The residue was diluted with dichloromethane washed twice with water The combined water phases were extracted with dichloromethane The combined dichloromethane phases were washed with diluted sodium hydrogen carbonate solution dried with sodium sulphate concentrated The oily crude was purified by column chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-fluoro-2-(trifluoromethyl)benzoic acid (2.0 g, 9.62 mmol, Aldrich) in a mixture of chloroform and methanol (1:1, 40 ml) was added a 2 M solution of TMS-diazomethane in ether (approximately 8 ml) dropwise, in portions over about 1 h, allowing the solution to cool down between additions. The solution was evaporated in vacuo. To the residue was added chloroform (approximately 40 ml) and the solvent removed in vacuo to give methyl 5-fluoro-2-(trifluoromethyl)benzoate as a colourless slightly cloudy oil (2.09 g). To a stirred solution of phenol (1.06 g, 11.3 mmol, Aldrich) in DMSO (8 ml) under nitrogen was added potassium t-butoxide (1.27 g, 11.3 mmol) and the mixture stirred to dissolve. To the mixture was added methyl 5-fluoro-2-(trifluoromethyl)benzoate (2.09 g, 9.41 mmol) in DMSO (2 ml) and the mixture allowed to stand for one week. To the dark coloured mixture was added dilute aqueous sodium bicarbonate and the mixture extracted with ether four times. The combined organic extracts were dried (Na2SO4), filtered and the solvent removed in vacuo to leave a yellow oil (approximately 2 g). The residue was purified on silica 50 g using 0-100% DCM-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give methyl 5-(phenyloxy)-2-(trifluoromethyl)benzoate as a colourless oil (0.516 g). to cool down between additions The solution was evaporated in vacuo To the residue was added chloroform (approximately 40 ml) the solvent removed in vacuo

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 4.48 g (22.5 mmol) 5-Fluoro-2-trifluoromethyl-benzoic acid methyl ester (Rarechem) and 60.0 ml dimethylsulphoxid were added 2.23 g (27.0 mmol) dimethylamine hydrochloride and 6.54 g (47.3 mmol) potassium carbonate. The reaction mixture was stirred for 8 h at 60° C. in an autoclave and was reduced with high vacuum rotation evaporator at 65° C. The residue was diluted with dichloromethane, washed twice with water. The combined water phases were extracted with dichloromethane. The combined dichloromethane phases were washed with diluted sodium hydrogen carbonate solution, dried with sodium sulphate and concentrated. The oily crude was purified by column chromatography and the desired product 15a was obtained in 72% yield (4.00 g, 16.2 mmol). was reduced with high vacuum rotation evaporator at 65° C The residue was diluted with dichloromethane washed twice with water The combined water phases were extracted with dichloromethane The combined dichloromethane phases were washed with diluted sodium hydrogen carbonate solution dried with sodium sulphate concentrated The oily crude was purified by column chromatography