(2-Acetamidophenyl) cyclohexyl methanone → (2-Aminophenyl)(cyclohexyl)methanone

Participants

Reaction Steps

A solution of (2acetamidophenyl) cyclohexyl methanone (0.53 g, 2.16 mmol) in methanol (5 ml) and concentrated hydrochloric acid (15 ml) was heated at 80° C. for 1 h. After this time the solution was cooled to ambient temperature and the solvents removed in vacuo. The residue was dissolved in water (10 ml) and basified with 4N sodium hydroxide solution (20 ml). The mixture was then extracted into ethyl acetate, (4×20 ml) and the organic layers combined and dried (MgSO4). The solvent was evaporated and the residue chromatographed on silica gel using petrol:ethyl acetate (2:1), to afford the amine (0.40 g, 91%) as a white solid. mp 73°-75° C. 1H NMR (360 MHz, CDCl3) δ 1.23-2.09 (10H, m), 3.27 (1H, m), 6.29 (2H, brs), 6.64 (2H, m), 7.25 (1H, dt, J=6 and 1 Hz), 7.76 (1H, dd, J=7 and 1 Hz). An alternative procedure could be used for preparation of (2-aminophenyl) cyclohexyl methanone: To a cooled (0° C.) and stirred solution of 2-aminobenzonitrile (59.5 g, 0.5 mol) in anhydrous diethyl ether (210 ml) was added dropwise cyclohexylmagnesium chloride (2M in diethyl ether, 700 ml) at such a rate as to maintain the temperature below 25° C. After a further 18 h stirring at room temperature, the mixture was cooled to -60° C. and treated dropwise (CAUTION! highly exothermic reaction) with 5N hydrochloric acid (600 ml). The mixture was then allowed to warm to room temperature, diluted. with additional 5N hydrochloric acid (500 ml) and the ethereal layer was separated. The acidic aqueous solution was basified to pH 4-5 with solid potassium hydroxide and then extracted with ethyl acetate (3×700 ml). The ethereal and ethyl acetate. solutions were combined, washed with brine (1000 ml), dried (MgSO4) and concentrated under vacuum to give the title compound (97 g, 94%) as a pale yellow solid.

Provenance & Evidence