Hydrochloric Acid → HCID 67282310, compound

Participants

Reaction Conditions

Reaction Steps

In each of three parallel synthesis tubes equipped with a magnetic stir bar was placed 5-hydroxy-1-methyl-2-(2,2,2-trifluoro-1-hydroxy-ethyl)-1H-pyridin-4-one (0.50 g, 2.24 mmol), a 36.5% by wt formaldehyde solution (6 mL, 80.4 mmol), and a 6.00 N sodium hydroxide solution (0.45 mL, 2.7 mmol). The resulting solution was heated to about 40° C. for overnight. Analysis by HPLC Method 1 (Example 24) indicated consumption of the starting material. The contents of the three tubes were combined, and the resulting solution was cooled in an ice-water bath. A 6.00 N hydrochloric acid solution (1.1 mL, 6.6 mmol) was added to adjust the pH of the solution to about 6. The mixture was concentrated in vacuo to remove most of the solvent to give a solid/liquid mixture. To the mixture was added methanol (100 mL), and the mixture was stirred for 1 h. The first crop of the solid was collected by suction filtration and washed with de-ionized water thoroughly to give 3-hydroxy-2-hydroxymethyl-1-methyl-6-(2,2,2-trifluoro-1-hydroxy-ethyl)-1H-pyridin-4-one (0.83 g, 48% yield, HPLC Method 1 (Example 24), RT=7.7 min, HPLC purity (peak percent area): 99.2% at λ=280 nm). 1H NMR (DMSO-d6+D2O) δ ppm: 6.53 (s, 1H), 5.54 (q, J=6.5 Hz, 1H), 4.67 (s, 2H), 3.76 (s, 3H); MS-ESI (m/z) 254.1 [M+1]+, 236.1, 208.1 (100%), 139.2.

Provenance & Evidence