Triethylamine hydrochloride → 1-(2,2-difluoroethyl)-5-hydroxy-2-methylpyridin-4(1H)-one

Participants

Reaction Steps

In a similar manner as described in example 4(a), 5-(benzyloxy)-1-(2,2-difluoroethyl)-2-methylpyridin-4(111)-one (2.20 g) was prepared from a mixture of 5-(benzyloxy)-2-methyl-4H-pyran-4-one (3.00 g, 13.8 mmol), difluoroethylamine (2.48 g, 55.2 mmol), triethylamine hydrochloride (5.58 g, 55.2 mmol) and pyridine (15 mL). Yield=58%; 1H NMR (90 MHz, MeOD-D4) δ (ppm): 7.53 (s, 1H), 7.27-7.45 (m, 5H), 6.36 (s, 1H), 5.56-6.77 (tt, J=54.9, 3.6 Hz, 1H), 5.04 (s, 2H), 4.24-4.60 (td, J=14.9, 2.7, 2H) and 2.36 (s, 3H); MS m/z 280 [M+1]+. (b) In a similar manner as described in example 1(b), 1-(2,2-difluoroethyl)-5-hydroxy-2-methylpyridin-4(111)-one (230 mg) was prepared from 5-(benzyloxy)-1-(2,2-difluoroethyl)-2-methylpyridin-4(1H)-one (500 mg, 1.80 mmol) with 10% Pd/C (wet, 50 mg) in methanol (40 mL) under hydrogen at 15 psi pressure in a Parr apparatus for 27 minutes. Yield=99%; 1H NMR (MeOD-D4, 90 MHz) δ (ppm): 7.46 (s, 1H), 6.37 (s, 1H), 5.62-6.83 (tt, J=54.9, 3.6 Hz, (1H), 4.26-4.60 (td, J=15.3, 2.4 Hz, 2H) and 2.38 (s, 3H); MS m/z 190 [M+1]+.

Provenance & Evidence