Formaldehyde → 3-hydroxy-2-(hydroxymethyl)-6-methyl-1-(2,2,2-trifluoroethyl)pyridin-4(1H)-one

Participants

Reaction Conditions

Reaction Steps

5-Hydroxy-2-methyl-1-(2,2,2-trifluoroethyl)pyridin-4(1H)-one hydrochloride (4.87 g. 20.0 mmol) was mixed with 37% formaldehyde (30 mL) and 6N sodium hydroxide (7 mL, 42.0 mmol). The reaction mixture was stirred at 39-42° C. for 11 hours, and then additional 37% formaldehyde (30 mL) was added. The reaction mixture was stirred at 37° C. for 12 hours and then left at room temperature for a further 12 hours. The solid was filtered and the filtrate was acidified to pH about 5 to 6. The solution was concentrated with silica gel and the product was purified by column chromatography with a gradient mixture of 5-10% methanol in ethyl acetate as eluant to give the title compound 3-hydroxy-2-(hydroxymethyl)-6-methyl-1-(2,2,2-trifluoroethyl)pyridin-4(1H)-one (3.02 g) as pale-peach solid. Yield 63.5%; 1H NMR (DMSO-D6+D2O, 90 MHz) δ (ppm): 6.20 (s, 1H), 5.15 (q, J=8.8 Hz, 2H), 4.33-4.92 (m, 2H) and 2.37 (s, 3H); MS m/z 238 [M+1]+.

Provenance & Evidence