反应详情

6.5 mL of ethanol and 6.5 mL of THF were added to 0.47 g (12.5 mmol, 8 eq) of sodium borohydride. 0.7 g (6.27 mmol, 4 eq) of calcium chloride was added at 4˜5° C., and the mixture was stirred at 4˜5° C. for 35 minutes. 1 g (1.57 mmol) of tert-butyl (3S)-3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate was added at 5° C. The mixture was stirred at 23˜29° C. for 6 hours. 35 mL of water was added dropwise. 12.5 mL of 1N hydrochloric acid was added dropwise, diluted with 20 mL of ethyl acetate, and the layers were separated. The aqueous layer was re-extracted with 20 mL of ethyl acetate. The organic layers were combined, and washed successively with 10 mL of water and 10 mL of an aqueous saturated sodium chloride solution. After concentrated under reduced pressure, the concentration residue was dissolved in 1 mL of ethanol, and allowed to stand overnight. Crystals were filtered, and washed with 0.2 mL of ethanol. The filtrate was concentrated under reduced pressure, 0.5 mL of ethyl acetate and 1 mL of IPE were added to the concentration residue, crystals were loosened, filtered, and washed with 0.75 mL of ethyl acetate/IPE=1/10.75 ml. Vacuum drying (40° C.) to a constant weight afforded 0.5 g of 6-[(1S)-1,3-dihydroxy-1-(1-trityl-1H-imidazol-4-yl)propyl]-N-methyl-2-naphthamide (yield 61%).

1. stirringThe mixture was stirred at 23˜29° C. for 6 hours
2. customthe layers were separated
3. extractionThe aqueous layer was re-extracted with 20 mL of ethyl acetate
4. washwashed successively with 10 mL of water and 10 mL of an aqueous saturated sodium chloride solution
5. concentrationAfter concentrated under reduced pressure
6. dissolutionthe concentration residue was dissolved in 1 mL of ethanol
7. waitto stand overnight
8. filtrationCrystals were filtered
9. washwashed with 0.2 mL of ethanol
10. concentrationThe filtrate was concentrated under reduced pressure, 0.5 mL of ethyl acetate and 1 mL of IPE
11. additionwere added to the concentration residue, crystals
12. filtrationfiltered
13. washwashed with 0.75 mL of ethyl acetate/IPE=1/10.75 ml
14. customVacuum drying (40° C.) to a constant weight