Trifluoroacetic acid → 4-ethoxy-3-methyl-N-(4-oxocyclohexyl)benzenesulfonamide

Participants

Reaction Steps

Trifluoroacetic acid (13.13 ml, 170 mmol) was added via addition funnel to solution of tert-butyl 4-oxocyclohexylcarbamate (1.817 g, 8.52 mmol) in DCM (34.1 ml) at room temperature. The reaction was stirred 3.5 hours then concentrated and the residue was placed under vacuum for 30 minutes. The residue was suspended in DCM (34.1 ml) and cooled in ice/water bath. N-methylmorpholine (20.61 ml, 187 mmol) was added followed by solid 4-ethoxy-3-methylbenzenesulfonyl chloride (2.0 g, 8.52 mmol) and the ice/water bath was removed. After stirring for 70 hours, LCMS indicated some product mass. The reaction was placed in water bath and pH adjust to 3 using 3N hydrochloric acid (aq). The resulting layers were separated, and the aqueous extracted second time with dichloromethane. The combined organics were dried over sodium sulfate to yield 2.9 g of a crude oil. TLC (50% ethyl acetate in heptane): indicated a major product at Rf=0.40, with minor spots at Rf=0.58 and Rf=0.12. The crude was chromatograph on Biotage 40M by TLC generated gradient to yield 4-ethoxy-3-methyl-N-(4-oxocyclohexyl)benzenesulfonamide (650 mg, 2.087 mmol). LCMS [M+H]=312.3.

Provenance & Evidence