Sulfuric Acid → 4-(Methylsulfonyl)phenol

Participants

Reaction Steps

Trans-4-(Aminomethyl)-cyclohexanecarboxylic acid (0.94 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 as an orange oil with 4-(methylsulfonyl)phenol as an impurity. Tert-butyl methyl ether (10 mL) and methylcyclohexane (5 mL) were added and the mixture was heated at 50° C. for 10 minutes. The mixture was then cooled to 40° C. over a period of 2 hours. The crystallization solution was seeded with 4-({[(2-methylpropanoyloxy)ethoxy]carbonylamino}methyl)cyclohexanecarboxylic acid (10 mg) and then stirred for 2 hours. The white, thick slurry was filtered and dried under vacuum at room temperature to provide 1 g of the title compound E2.

Provenance & Evidence