Ethyl phenylacetate → HCID 67357346, compound

Participants

Reaction Steps

3-Methyl-3-phenylpiperidin-2-one is prepared using the procedures described in Examples 91A and 91B substituting ethyl 2-phenylpropionate for ethyl 2-phenylacetate. To 3-methyl-3-phenylpiperidin-2-one (1.01 g, 5.34 mmol) in tetrahydrofuran (3 mL) was added potassium t-butoxide (1.0 Min tetrahydrofuran, 6.40 mL, 6.40 mmol), and the mixture was allowed to stir at room temperature for 30 minutes. To the mixture was added ethyl 2-bromoacetate (0.591 mL, 5.34 mmol). The reaction was heated to 60° C. and stirred for 2 hours. The reaction was cooled, diluted with ethyl acetate (50 mL), washed with 1 N HCl (25 mL) and brine (25 mL), dried over magnesium sulfate and concentrated. The residue was loaded directly onto a SF25-40 silica gel column (Analogix®, Burlington, Wis.), and the intermediate ethyl ester was eluted using a gradient of 5% ethyl acetate/hexanes to 75% ethyl acetate over 30 minutes (flow=30 mL/minute). The ethyl ester was dissolved in ethanol (10 mL) and sodium hydroxide (2.0 M, 5.34 mL, 10.67 mmol) was added. After stirring for 30 minutes, thin layer chromatography (100% ethyl acetate) showed complete consumption of the starting material. The reaction was diluted with ethyl acetate (50 mL), washed with 1 N HCl (50 mL) and brine (50 mL), dried over magnesium sulfate, and concentrated to give the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.42-7.11 (m, 5H), 4.28 (d, J=16.7, 1H), 4.12 (d, J=16.7, 1H), 3.59-3.33 (m, 2H), 2.23 (dt, J=4.5, 13.5, 1H), 2.07-1.89 (m, 1H), 1.85-1.66 (m, 2H), 1.61 (s, 3H); MS (APCI+) m/z 248 (M+H)+.

Provenance & Evidence