Sulfuric Acid → 4-(Methylsulfonyl)phenol

Participants

Reaction Steps

Pregabalin (0.95 g) and water (25 mL) were charged to a vessel at room temperature. Potassium carbonate (0.8 g) was added in one portion and the mixture was stirred at room temperature for 5 minutes. A solution of [4-(methylsulfonyl)phenoxycarbonyloxy]ethyl 2-methylpropanoate D3 (1.6 g) in acetonitrile (25 mL) was added. After 6 hours, tert-butyl methyl ether (50 mL) was added and the reaction mixture was cooled to 5-10° C. A solution of 5% aqueous sulfuric acid was added to adjust the pH to approximately 3. The mixture was then warmed to room temperature and stirred for 10 minutes. The organic layer was washed with water (3×10 mL) and evaporated to yield the title compound E1 as an orange oil with 4-(methylsulfonyl)phenol impurity. The crude product was purified by silica gel chromatography using ethyl acetate and hexane (4:6) to provide 1 g of the title compound E1 as a viscous oil.

Provenance & Evidence