Hydrochloric Acid → (3,5-Difluoropyridin-2-YL)methanol

Participants

Reaction Conditions

Reaction Steps

3,5-difluoro-2-pyridinecarboxylic acid (ALFAAESAR, 300 mg, 1.886 mmol) was dissolved in tetrahydrofuran (THF) (10 mL). N,N-diethylethanamine (FLUKA, 0.549 mL, 3.96 mmol) was added and mixture was cooled to −10° C. (ice in acetone). Isobutyl chloroformate (0.269 mL, 2.074 mmol, FLUKA) was added dropwise. Reaction was stirred 20 min at −10° C. Mixture was filtered into a previously prepared solution of sodium borohydride (ALDRICH, 214 mg, 5.66 mmol) in 2 mL of water at 0° C. and was stirred at 0° C. for 45 min. HCl (1N, aq) was added slowly until neutral pH. Aqueous mixture was partitioned with DCM (3×15 ml). Organic layer was dried over Na2SO4 (anh), filtered and concentrated. Residue was purified by silica gel chromatography using a linear gradient of DCM/MeOH to yield title compound (3,5-difluoro-2-pyridinyl)methanol (116 mg, 0.799 mmol, 42.4% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm: 8.44-8.45 (s, 1H), 7.88-7.93 (m, 1H), 5.35 (t, 1H), 4.56-4.58 (m, 2H). [ES+MS] m/z 146 (MH+).

Provenance & Evidence