5,6-Dichloronicotinic acid → (5,6-Dichloropyridin-3-yl)methanol

Participants

Reaction Conditions

Reaction Steps

A slurry of 5,6-dichloronicotinic acid (25.3 g, 132 mmol) in THF (30 mL, 4.4 M) is cooled to 0° C. and carefully treated with 2 M borane dimethyl sulfide/THF (100 mL, 200 mmol) via syringe under a stream of nitrogen. After 1 h, the cooling bath is removed. After stirring overnight the colution is re-cooled to 0° C. and carefully quenched with water (20 mL). The reaction volume is reduced in vacuo, 50% NaHCO3 (150 mL) is added and the mixture is extracted with ethyl acetate (2×150 mL). The organic layer is washed with saturated aq NaCl (100 mL) and dried over Na2SO4. The product is purified by MPLC (30-90% ethyl acetate in n-heptane) to provide 5,6-dichloro-pyridin-3-yl-methanol as a white solid (19.1 g, 81%): Rf 0.57 (25% ethyl acetate in n-heptane), 1H NMR (CDCl3, 300 MHz) δ 8.27 (d, J=2.3 Hz, 1 H), 7.84 (d, J=2.3 Hz, 1 H), 4.74 (s, 2 H); ESI-LCMS m/z calcd for C6H5Cl2NO: 177.0; found 178.0 (M+1)+.

Provenance & Evidence