3-phenylpiperidin-2-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of the product from Example 91B (1.08 g, 6.16 mmol) in tetrahydrofuran (10 mL) at 0° C. was added potassium tert-butoxide (1.0 Min tetrahydrofuran) (6.78 mL, 6.78 mmol). After stirring for 20 minutes, ethyl 2-bromoacetate (0.750 mL, 6.78 mmol) was added, and the reaction was allowed to warm to room temperature. After stirring for 3 hours, the reaction was poured in ethyl acetate/water (1:1, 200 mL). The organic layer was washed with brine (100 mL), dried over magnesium sulfate and concentrated. Silica gel chromatography using a GraceResolv 80 g silica gel column (Grace Davison Discovery Sciences) eluting with a gradient of 25% ethyl acetate/hexanes to 85% ethyl acetate/hexanes (flow=40 mL/minute) over 30 minutes supplied the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.39-7.14 (m, 5H), 4.45 (d, J=17.2, 1H), 4.23 (q, J=7.1, 2H), 3.91 (d, J=17.2, 1H), 3.78-3.65 (m, 1H), 3.65-3.49 (m, 1H), 3.41 (dt, J=5.7, 11.3, 1H), 2.32-2.12 (m, 1H), 2.12-1.74 (m, 3H), 1.30 (t, J=7.2, 3H). After stirring for 3 hours The organic layer was washed with brine (100 mL) dried over magnesium sulfate concentrated eluting with a gradient of 25% ethyl acetate/hexanes to 85% ethyl acetate/hexanes (flow=40 mL/minute) over 30 minutes

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of the product from Example 91A (2.42 g, 11.14 mmol) in 7 M ammonia/methanol (40 mL) was added to solvent washed Raney®-nickel (24.20 g, 412 mmol) in a 250 mL stainless steel pressure bottle and stirred for 16 hours under hydrogen at 30 pounds per square inch at room temperature. The mixture was filtered through a nylon membrane and concentrated to supply the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.39-7.17 (m, 5H), 6.00 (s, 1H), 3.65 (dd, J=6.2, 8.3, 1H), 3.54-3.32 (m, 2H), 2.33-2.10 (m, 1H), 2.06-1.70 (m, 3H); MS (ESI+) m/z 176.1 (M+H)+. The mixture was filtered through a nylon membrane concentrated to supply the title compound