反应详情

温度

-10 °C

To a solution of anhydrous calcium chloride (1.86 g, 16.3 mmol) in ethanol (32 mL) were added sodium borohydride (1.27 g, 33.6 mmol) and ethanol (5 mL) at −10° C., and the mixture was stirred at −10° C. for 30 min. To the reaction mixture was added dropwise a solution of ethyl (3S)-3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-tosyl-1H-imidazol-4-yl)propanoate (2.5 g, 5.6 mmol) in tetrahydrofuran (73 mL)/ethanol (10 mL), and tetrahydrofuran (5 mL) at −10° C. The obtained reaction mixture was stirred at 7° C. for 21 hr, and to the obtained reaction mixture were added dropwise water (100 mL), 1 mol/L hydrochloric acid (40 mL) and ethyl acetate (200 mL) at 10° C. or below, and the mixture was stirred. To the separated organic layer was added 0.2 mol/L hydrochloric acid (14 mL) at 5° C., and the mixture was stirred. The reaction mixture was adjusted to pH 7.5 with 0.5 mol/L aqueous sodium hydroxide solution at 5° C. To the separated organic layer was added again 0.2 mol/L hydrochloric acid (14 mL) at 5° C., and the mixture was stirred. The reaction mixture was adjusted to pH 7.5 with 0.5 mol/L aqueous sodium hydroxide solution at 5° C. To the separated organic layer was added water (10 mL), and the mixture was adjusted to pH 9.5 with 0.5 mol/L aqueous sodium hydroxide solution. To the separated organic layer was added water (120 mL), and the mixture was heated to 60° C., and stirred for 3 hr. The separated organic layer was concentrated at 60° C. under reduced pressure to give 6-[(1S)-1,3-dihydroxy-1-(1H-imidazol-4-yl)propyl]-N-methyl-2-naphthamide (2.3 g, 7.0 mmol).

1. customThe obtained reaction mixture
2. stirringwas stirred at 7° C. for 21 hr
3. customto the obtained reaction mixture
4. stirringthe mixture was stirred
5. stirringthe mixture was stirred
6. stirringthe mixture was stirred
7. temperaturethe mixture was heated to 60° C.
8. stirringstirred for 3 hr
9. concentrationThe separated organic layer was concentrated at 60° C. under reduced pressure