Acetic Acid → {4-[(4-Bromo-phenylamino)-methyl]-tetrahydro-pyran-4-yl}-carbamic acid tert-butyl ester

Participants

Reaction Steps

A solution of (4-formyl-tetrahydro-pyran-4-yl)-carbamic acid tert-butyl ester (4.48 g, 19.5 mmol), 4-bromoaniline (3.38 g, 19.7 mmol), and acetic acid (1.2 mL, 21.2 mmol) in ethyl acetate (50 mL) contained in a 250 mL round bottom flask fitted with a reflux condenser and a Dean and Stark trap was heated at reflux under N2 blanket for 2 h then cooled to ambient temperature. Sodium cyanoborohydride (1.29 g, 19.5 mmol) was added and the mixture stirred over night. The reaction mixture was then washed with water (50 mL), saturated aqueous sodium chloride (50 mL), dried (MgSO4), preabsorbed on silica gel and flash chromatographed (elution solvent: 10% (v/v) ethyl acetate/hexane) to isolate the desired product as 3.1 g of white solid foam. LRMS (ESI) m/z 385.0, 387.0 [(M+H)+, calcd for C17H26N2O3Br 386.3].

Provenance & Evidence