Hydrochloric Acid → 6-[(1S)-1,3-dihydroxy-1-(1-phenylsulfonyl-1H-imidazol-4-yl)propyl]-N-methyl-2-naphthamide

Participants

Reaction Conditions

Reaction Steps

To a solution of anhydrous calcium chloride (0.84 g, 7.4 mmol) in ethanol (9 mL) was added sodium borohydride (0.57 g, 14.8 mmol) at −15° 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-phenylsulfonyl-1H-imidazol-4-yl)propanoate (1.5 g, 3.0 mmol) in tetrahydrofuran (75 mL)/ethanol (15 mL) at −10° C. The obtained reaction mixture was stirred at 5° C. for 8 hr, and to the obtained reaction mixture were added dropwise water (12 mL), 1 mol/L hydrochloric acid (15 mL) and ethyl acetate (30 mL) at 10° C. or below, and the mixture was stirred. To the separated organic layer was added 0.2 mol/L hydrochloric acid (15 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 (15 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 (15 mL), and the mixture was adjusted to pH 9.5 with 0.5 mol/L aqueous sodium hydroxide solution. The separated organic layer was washed with 10 w/v % brine (15 mL). To the separated organic layer was added water (18 mL), and the mixture was heated to 60° C., and stirred for 3 hr. The separated organic layer was concentrated under reduced pressure to give 6-[(1S)-1,3-dihydroxy-1-(1-phenylsulfonyl-1H-imidazol-4-yl)propyl]-N-methyl-2-naphthamide (1.2 g, 2.5 mmol). yield 83%. enantiomeric excess: 62% ee.

Provenance & Evidence