HCID 67282712, compound → HCID 67282524, compound

To a clear solution of 3-benzyloxy-5-(1-chloro-2,2,2-trifluoro-ethyl)-2-methyl-1H-pyridin-4-one hydrochloric acid salt (2.03 g, 5.50 mmol) in methanol (70 mL) was added sodium borohydride (1.25 g, 33.0 mmol) in several portions. The reaction was completed within 20 min. The reaction mixture was quenched with deionized water (80 mL). The volume of the resulting clear solution was reduced to about 10 mL by evaporation under reduced pressure to give a solid/liquid mixture. Another 50 mL of deionized water was added. The aqueous solution was extracted with dichloromethane (3×50 mL). The combined organic fractions was dried over Na2SO4, filtered, then concentrated in vacuo to give an oil (1.3 g), which solidified upon standing. HPLC analysis (HPLC Method 1, Example 24) of the crude solid material indicated presence of a mixture of the desired compound 3-benzyloxy-2-methyl-5-(2,2,2-trifluoro-ethyl)-1H-pyridin-4-one (RT=14.7 min, peak percent area=80.6%) and 3-benzyloxy-2-methyl-5-(2,2,2-trifluoro-1-methoxy-ethyl)-1H-pyridin-4-one (RT=15.7 min, peak percent area=16.2%) in about 5/1 ratio. Purification of the solid by column chromatography on silica gel (methanol/dichloromethane 2/100 to 3/100 v/v as eluant) afforded the title compound (0.9 g, 56% yield, HPLC purity (peak percent area): 98% at λ=280 nm). 1H NMR (DMSO-d6) δ ppm: 11.47 (br s, 1H), 7.60 (s, 1H), 7.37 (m, 5H), 5.06 (s, 2H), 3.41 (q, J=11.5 Hz, 2H), 2.06 (s, 3H); MS-ESI (m/z) 298.2 [M+1]+, 91.1 (100%).