1-(1-benzylpiperidin-4-yl)-3H-indol-2-one

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

Procedure: A solution of 10 ml of methanol containing 296 mg of 1-(1-benzyl-4-piperidyl)indol-2-one was treated with 300 mg of palladium hydroxide catalyst. The resulting suspension was hydrogenated at atmospheric pressure for 60 minutes at 23° C. More catalyst was added (100 mg) and the hydrogenation was continued for 30 minutes more. The reaction mixture was filtered through Celite, concentrated and azeotropically dried with toluene to yield 217 mg of 1-(4-piperidyl)indol-2-one. More catalyst was added (100 mg) the hydrogenation was continued for 30 minutes The reaction mixture was filtered through Celite concentrated azeotropically dried with toluene

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

Procedure: To a solution of 200 ml of methanol containing 2-aminophenylacetic acid (13.8 mmole), 1.82 ml (15.2 mmole) 1-benzyl-4-piperidone, and 4 ml acetic acid was added 20 g of 3 Angstrom molecular sieves and 1.91 g (30.4 mmole) of sodium triacetoxyborohydride at room temperature. The reaction mixture was protected from moisture and stirred overnight. After 12 hours, an additional 500 mg of sodium triacetoxyborohydride was added and stirring was continued for 4 hours more. Saturated sodium bicarbonate solution was added and most of the methanol was removed under reduced pressure. The aqueous solution was neutralized with acetic acid and extracted with ethyl acetate solution. The combined extracts were dried (sodium sulfate) and concentrated. Chromatography of the crude reaction product on silica gel (chloroform-methanol-concentrated ammonium hydroxide elution, 96:4:0.4, v/v) afforded 296 mg of a waxy solid. This material was dissolved in a solution of methanol and ether and treated with HCl gas. The resulting precipitate was collected, washed with ether and dried to give the title compound as a solid: m.p. 266°-270° C. After 12 hours stirring was continued for 4 hours was removed under reduced pressure extracted with ethyl acetate solution The combined extracts were dried (sodium sulfate) concentrated Chromatography of the crude reaction product on silica gel (chloroform-methanol-concentrated ammonium hydroxide elution, 96:4:0.4, v/v) afforded 296 mg of a waxy solid The resulting precipitate was collected washed with ether dried