反应详情

温度

80 °C

To a solution of 6-(2,2,2-trichloro-acetyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid ethyl ester (Comp. No. 4a) (1 g, 2.94 mmol) in anhydrous tetrahydrofuran (9 ml) was added (R)-1-(2,4-difluoro-phenyl)-propylamine (0.5 g, 2.94 mmol) and triethylamine (1.22 ml, 8.8 mmol). The resulting mixture was stirred for 24 h, then another portion of (R)-1-(2,4-difluoro-phenyl)-propylamine (0.05 g) and triethylamine (0.8 ml) was added. The mixture was stirred for 2 days and then evaporated to dryness. To the residue was added 50 ml water, 50 ml methanol and potassium hydroxide (0.84 g, 15 mmol) and the mixture was heated to 80° C. for 15 h. A further portion of potassium hydroxide (0.84 g) was added and the mixture was heated to 80° C. for 17 h. After evaporation of methanol, dilution with 70 ml water and acidification with excess aqueous 2 N hydrochloric acid, the precipitate was filtrated and washed with 50 ml water to give 0.65 g (60% over 2 steps) of 6-[(R)-1-(2,4-difluoro-phenyl)-propylcarbamoyl]-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid as yellowish powder. LC/MS (method 4): Rt=1.19 min; m/z=365.1 (M+H+).

1. stirringThe mixture was stirred for 2 days
2. customevaporated to dryness
3. temperaturethe mixture was heated to 80° C. for 17 h
4. customAfter evaporation of methanol, dilution with 70 ml water and acidification with excess aqueous 2 N hydrochloric acid
5. filtrationthe precipitate was filtrated
6. washwashed with 50 ml water