反应详情

To a solution of 50 g of (R)-(+)-2-oxo-3-tert-butoxycarbonylamino-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine as described in WO98/25911 in 43.3 g of acetic acid were added 70.8 g of cyclohexanone and 1.5 g of platinum oxide. The resulting mixture was stirred at room temperature for 5 hours under pressure of 3 to 3.5 kg/cm2 in a hydrogen gas atmosphere. To the reaction mixture were added 200 ml of ethyl acetate and 5 g of active charcoal, followed by stirring for further 1 hour at room temperature. The reaction mixture was filtered. A 2N aqueous solution of sodium hydroxide was added dropwise to the filtrate to neutralize the same under stirring and then, it was separated into layers. The organic layer was successively washed with a saturated aqueous solution of sodium bicarbonate and brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. To the residue were added 200 ml of ethanol and 200 ml of water. The mixture was stirred at 50° C. for 1 hour and then for 2 hours under ice cooling. Crystals so precipitated were collected by filtration with suction, washed with a mixed solvent of ethanol and water (1:1) and then dried to obtain 59.3 g of the title compound.

1. filtrationThe reaction mixture was filtered
2. additionA 2N aqueous solution of sodium hydroxide was added dropwise to the filtrate
3. stirringunder stirring
4. customit was separated into layers
5. washThe organic layer was successively washed with a saturated aqueous solution of sodium bicarbonate and brine
6. dry with materialdried over anhydrous sodium sulfate
7. customThe solvent was evaporated under reduced pressure
8. additionTo the residue were added 200 ml of ethanol and 200 ml of water
9. stirringThe mixture was stirred at 50° C. for 1 hour
10. waitfor 2 hours under ice cooling
11. customCrystals so precipitated
12. filtrationwere collected by filtration with suction
13. washwashed with a mixed solvent of ethanol and water (1:1)
14. customdried