Sodium borohydride → 6-Hydroxymethyl-nicotinic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

Diisobutylaluminum hydride (1.5 M solution in toluene, 9.82 mL) was added dropwise to a solution of 6-(methoxy-methyl-carbamoyl)-nicotinic acid methyl ester (1.1 g, 4.91 mmol) in THF (50 mL) at −78° C. over 10 minutes. The reaction mixture was stirred for 2 hours at −78° C., quenched with 5% HCl/ethanol and warmed to room temperature. The reaction mixture was concentrated in vacuo and the resulting residue was taken up in saturated K2CO3 and extracted with ethyl acetate (2×). The combined organic extracts were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. MeOH (15.0 mL) was added to the crude reaction mixture and cooled to 0° C. Sodium borohydride (0.280 g, 7.20 mmol) was added in two portions to the reaction mixture and stirred at 0° C. for 30 minutes. Additional sodium borohydride (0.136 g, 3.6 mmol) was added to the reaction mixture, warmed to room temperature and stirred for 2 hours. The reaction mixture was diluted with dichloromethane (75.0 mL), washed with water and saturated NaHCO3, dried (Na2SO4), filtered and evaporated to yield 6-hydroxymethyl-nicotinic acid methyl ester (0.400 g, 49% yield) as a solid.

Provenance & Evidence