ethyl 2,2-difluoro-2-(4-fluorophenoxy)acetate

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2,2-difluoro-2-(4-fluorophenoxy)acetic acid ethyl ester (2.9 g, 12 mmol) in a mixture of MeOH (20 ml) and THF (10 ml) was added a solution of NaOH (1.48 g, 37 mmol) in water (10 ml). The reaction mixture was stirred 20 h at rt and 1 h at 40° C. The reaction mixture was concentrated and the remaining aqueous solution was diluted with water (10 ml) and washed with hexanes. The solution was acidified to pH 3 by adding 1N HCl and the heterogeneous mixture was extracted with ethyl acetate. The combined extracts were washed with brine and after drying over sodium sulfate, the solvent was removed to obtain 2,2-difluoro-2-(4-fluorophenoxy)acetic acid as The reaction mixture was concentrated the remaining aqueous solution was diluted with water (10 ml) washed with hexanes by adding 1N HCl the heterogeneous mixture was extracted with ethyl acetate The combined extracts were washed with brine after drying over sodium sulfate the solvent was removed

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2,2-difluoro-2-(4-fluorophenoxy)acetic acid ethyl ester (2.9 g, 12 mmol) in a mixture of MeOH (20 ml) and THF (10 ml) was added a solution of NaOH (1.48 g, 37 mmol) in water (10 ml). The reaction mixture was stirred 20 h at rt and 1 h at 40° C. The reaction mixture was concentrated and the remaining aqueous solution was diluted with water (10 ml) and washed with hexanes. The solution was acidified to pH 3 by adding 1N HCl and the heterogeneous mixture was extracted with ethyl acetate. The combined extracts were washed with brine and after drying over sodium sulfate, the solvent was removed to obtain 2,2-difluoro-2-(4-fluorophenoxy)acetic acid as The reaction mixture was concentrated the remaining aqueous solution was diluted with water (10 ml) washed with hexanes by adding 1N HCl the heterogeneous mixture was extracted with ethyl acetate The combined extracts were washed with brine after drying over sodium sulfate the solvent was removed

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

実験手順: A suspension of 60% of NaH in oil (3.84 g, 96 mmol) was washed three times with hexanes and the solid was suspended in dry DMF (80 ml). 4-Fluorophenol (8.96 g, 80 mmol) was slowly added over a period of 5 min and the reaction mixture was stirred at rt for about 10 min. The reaction mixture was cooled at 0° C. and 2-bromo-2,2-difluoroacetic acid ethyl ester (16.24 g, 80 mmol) was slowly added. The reaction mixture was heated at 90° C. for 20 h. After allowing the reaction to reach room temperature, ethyl ether (300 ml) was added and the suspension was washed with water and brine. After drying the organic layer over sodium sulfate for 15 min, the solvent was evaporated and the crude was purified by flash chromatography, using a mixture of ethyl acetate/hexanes (1/10) to give 2,2-difluoro-2-(4-fluorophenoxy)acetic acid ethyl ester as an oil (11.0 g, 59%). was washed three times with hexanes The reaction mixture was cooled at 0° C. The reaction mixture was heated at 90° C. for 20 h the reaction to reach room temperature the suspension was washed with water and brine After drying the organic layer over sodium sulfate for 15 min the solvent was evaporated the crude was purified by flash chromatography a mixture of ethyl acetate/hexanes (1/10)

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2,2-difluoro-2-(4-fluorophenoxy)acetic acid ethyl ester (2.9 g, 12 mmol) in a mixture of MeOH (20 ml) and THF (10 ml) was added a solution of NaOH (1.48 g, 37 mmol) in water (10 ml). The reaction mixture was stirred 20 h at rt and 1 h at 40° C. The reaction mixture was concentrated and the remaining aqueous solution was diluted with water (10 ml) and washed with hexanes. The solution was acidified to pH 3 by adding 1N HCl and the heterogeneous mixture was extracted with ethyl acetate. The combined extracts were washed with brine and after drying over sodium sulfate, the solvent was removed to obtain 2,2-difluoro-2-(4-fluorophenoxy)acetic acid as The reaction mixture was concentrated the remaining aqueous solution was diluted with water (10 ml) washed with hexanes by adding 1N HCl the heterogeneous mixture was extracted with ethyl acetate The combined extracts were washed with brine after drying over sodium sulfate the solvent was removed

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

実験手順: A suspension of 60% of NaH in oil (3.84 g, 96 mmol) was washed three times with hexanes and the solid was suspended in dry DMF (80 ml). 4-Fluorophenol (8.96 g, 80 mmol) was slowly added over a period of 5 min and the reaction mixture was stirred at rt for about 10 min. The reaction mixture was cooled at 0° C. and 2-bromo-2,2-difluoroacetic acid ethyl ester (16.24 g, 80 mmol) was slowly added. The reaction mixture was heated at 90° C. for 20 h. After allowing the reaction to reach room temperature, ethyl ether (300 ml) was added and the suspension was washed with water and brine. After drying the organic layer over sodium sulfate for 15 min, the solvent was evaporated and the crude was purified by flash chromatography, using a mixture of ethyl acetate/hexanes (1/10) to give 2,2-difluoro-2-(4-fluorophenoxy)acetic acid ethyl ester as an oil (11.0 g, 59%). was washed three times with hexanes The reaction mixture was cooled at 0° C. The reaction mixture was heated at 90° C. for 20 h the reaction to reach room temperature the suspension was washed with water and brine After drying the organic layer over sodium sulfate for 15 min the solvent was evaporated the crude was purified by flash chromatography a mixture of ethyl acetate/hexanes (1/10)