Sodium borohydride → (2,3-Dichloro-4-pyridinyl)methanol

Participants

Reaction Steps

2,3-Dichloro-N-methyl-isonicotinamide (0.353 g, 1.72 mmol) was stirred in 6 mL DCM (not quite homogeneous). tBuONO (0.412 mL, 3.44 mmol) was added followed by the addition of two drops of TFA. After 3 h an additional 0.600 ML tBuONO (5.00 mmol) and three drops TFA were added. The resulting solution was stirred an additional 16 h. An additional 0.400 mL tBuONO (3.34 mmol) and 2 drops TFA were added. After an additional 4.5 h an 0.600 mL tBuONO (5.00 mmol) and 3 drops TFA were added. The reaction was stirred 3 days and was quenched with half-sat NaHCO3 (aq). The mixture was extracted 3× with DCM. The organic phases were dried over Na2SO4, filtered, and concentrated. The slightly impure N-nitrosoamide (0.425 g, 1.82 mmol) was stirred in 5 mL THF. NaBH4 (0.137 g, 3.63 mmol) was added and after 2 h the reaction was slowly quenched with 1M HCl until the bubbling stopped. The solution pH was adjusted to pH 9 with Na2CO3 (s). The mixture was extracted 3× with EtOAc. The organic phases were dried over Na2SO4, filtered, and concentrated to afford the titled compound in good purity. 1H NMR (CDCl3) δ8.32 (d, 1H, J=4.8 Hz), 7.51 (d, 1H, J=5.0 Hz), 4.82 (s, 2H), 2.34 (bs, 1H).

Provenance & Evidence