Sulfuric Acid → 6-(1,1-Dioxido-4-thiomorpholinyl)-4-(4-fluoro-2-methylphenyl)nicotinamide

Participants

Reaction Conditions

Reaction Steps

A mixture of 5-cyano-4-(4-fluoro-2-methylphenyl)-2-(1,1-dioxo-thiomorpholin-4-yl)pyridine (14.80 g, 42.85 mmol), 15 mL of toluene, and 15 mL (27.6 g, 281 mmol) of concentrated sulfuric acid was heated in a 500-mL flask at 70° C. for 12 hours. The mixture was cooled and quenched with 150 mL cold H2O. A solution of 22.8 g (570 mmol) of sodium hydroxide in 200 mL of H2O was added dropwise at 25–30° C. over 15 minutes. The precipitate was filtered, washed with H2O, and dried to afford 15.68 g (100.7%) of 4-(4-fluoro-2-methylphenyl)-6-(1,1-dioxo-thiomorpholin-4-yl)pyridine-3-carboxamide as a colorless solid (2 wt % toluene remains).

Provenance & Evidence