Hydrochloric Acid → (2-Chloropyridin-4-yl)methanol

Participants

Reaction Steps

Carbonyldiimidazole (CDl, 7.88 g, 46.2 mmol, 1.5 equiv) is added at room temperature to a solution of 2-chloroisonicotinic acid (5.0 g, 30.8 mmol) in THF (70 ml). The reaction mixture is stirred at rt overnight, and then added dropwise to a cold (0° C.) solution of NaBH4 (6.07 g, 154 mmol, 5.0 eq) in water (175 ml). After stirring for 10 minutes at 0° C., HCl (2 M aqueous solution) is carefully added. Volatiles are removed via rotary evaporation, and the residue is dissolved in an aqueous 10% solution of NaHCO3. After five extractions with EtOAc, the combined organic layers are dried over Na2SO4, filtered and concentrated in vacuo. 1H-NMR analysis of the residue indicated adequate purity for direct use of the product (4.40 g, 99%) in the next step. 1H NMR (400 MHz, CDCl3): δ=8.37 (d, J=5.1 Hz, 1H), 7.39 (s, 1H), 7.23 (d, J=5.1 Hz, 1H), 4.78 (s, 2H). MS (ES+): 144 (M+H)+.

Provenance & Evidence