Hydrochloric Acid → 2,4-Dimethylpyrimidin-5-ol

Participants

Reaction Conditions

Reaction Steps

To a 22-Liter round bottomed flask was charged potassium tert-butoxide (1200 g, 11 mol, 3.5 equiv.) and 1-butanol (2700 mL). The mixture was stirred for 40 mins and then 1-decanethiol (1300 mL, 6.1 mol, 2.0 equiv.) was added. To the resulting slurry was added portionwise, 5-methoxy-2,6-dimethylpyrimidin-1-ium chloride (17, 532 g, 3.05 mol, 1.0 equiv.), using a minimal amount of 1-butanol for rinses as needed. The mixture was heated to 105-110° C. and stirred for 24 hours at this temperature. The mixture was cooled to room temperature and aqueous hydrochloric acid solution (6 N, 2000 mL) was added slowly, maintaining the internal temperature below 35° C. Heptane (2700 mL) was added and the mixture stirred for 10 mins. Stirring was halted and the phases were separated. The upper organic phase was backwashed with additional 6 N HCl solution (1000 mL). The aqueous phases were combined and neutralized by addition of aqueous sodium hydroxide solution (50% w/w, 789 mL) to pH=7-8, then extracted with 2-methyltetrahydrofuran (2×3000 mL) The 2-methyltetrahydrofuran was removed by vacuum distillation and replaced with heptane (3000 mL). The mixture was concentrated to near dryness and heptane (1300 mL was added). The resulting slurry was filtered and the wet cake was washed with heptane (3×400 mL). The cake was dried under vacuum with a nitrogen sweep to afford 2,4-dimethylpyrimidin-5-ol (18, 281 g, 74% yield) as an off-white solid.

Provenance & Evidence