Sodium borohydride → alpha-[1-[4-[4-(1,1-dimethylethyl)phenyl]-4-hydroxybutyl]-4-piperidinyl]-1-[(4-fluorophenyl)methyl]-1H-benzimidazole-2-methanol

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Reaction Steps

To a stirred, room temperature, solution of 1-[4-(1,1-dimethylethyl)phenyl]-4-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]carbonyl]-1-piperidinyl]-1-butanone (2.1 g, 3.9×10-3 mole) and methanol (80 ml) was added NaBH4 (0.42 g, 1.1×10-2 mole). After stirring overnight, the methanol was evaporated at reduced pressure. The concentrate was dissolved in a two phase mixture of EtOAc/H2O. The layers were separated and the aqueous layer was re-extracted with EtOAc. The EtOAc extracts were combined, washed with saturated aqueous NaCl, and dried over anhydrous MgSO4. The drying agent was removed by filtration and the filtrate was evaporated at reduced pressure leaving a solid. Crystallization from cyclohexane/hexane afforded α-[1-[4-[4-(1,1-dimethylethyl)phenyl]-4-hydroxybutyl]-4-piperidinyl]-1-[(4-fluorophenyl)methyl]-1H-benzimidazole-2-methanol as a colorless solid: 1.6 g (75%), m.p. 87-90° C.

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