反应详情

温度

-10 °C

A mixture of rac-2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-ylamino]-4-(trifluoromethyl)pyrimidine-5-carboxylic acid (2.0 g), 4-methyl morpholine (1.1 mL) and 1,2-dimethoxyethane (40 mL) was cooled to −10° C., isobutyl chloroformate (1.1 mL) was added thereto, and the mixture was stirred at the same temperature for 1 hour. The insoluble materials in the reaction mixture were filtered and washed with 1,2-dimethoxyethane. The filtrate was cooled to −60° C. and a solution of sodium borohydride (377 mg) in water (4.0 mL) was added thereto, followed by stirring as it is for 1 hour. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and then the residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=10:90 to 20:80) to obtain rac-{2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-ylamino]-4-(trifluoromethyl)pyrimidin-5-yl}methanol (1.05 g) as a colorless oily substance.

1. filtrationThe insoluble materials in the reaction mixture were filtered
2. washwashed with 1,2-dimethoxyethane
3. temperatureThe filtrate was cooled to −60° C.
4. additiona solution of sodium borohydride (377 mg) in water (4.0 mL) was added
5. stirringby stirring as it
6. waitis for 1 hour
7. additionTo the reaction mixture was added water
8. extractionfollowed by extraction with ethyl acetate
9. washThe organic layer was washed with water and saturated brine
10. dry with materialdried over anhydrous magnesium sulfate
11. customThe solvent was evaporated under reduced pressure
12. customthe residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=10:90 to 20:80)