4-benzyl-3,3-dimethylpiperazin-2-one

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of lithiulalluminium hydride (1.078 g, 28.4 mmol) in tetrahydrofuran (200 ml) at 0-20° C. was added 4-benzyl-3,3-dimethylpiperazin-2-one (6.2 g, 28.4 mmol in 100 ml tetrahydrofuran) over 1 h. The reaction mixture was warmed to 25° C. over 15 minutes followed by reflux for 6 h. The progress of reaction was monitored by TLC. After completion of reaction, the reaction mixture was cooled to 0-10° C. and 10% sodium hydroxide (50 ml) was added slowly over 1 h. and then allowed to stir for 20 hr at 25° C. The reaction mass was passed through celite and washed with tetrahydrofuran (500 ml). The combined filtrate was concentrated under reduced pressure. Water (100 ml) was added and the aq. phase was extracted with ethyl acetate (3×100 ml). The combined organic layer was washed with brine (50 ml) and dried over sodium sulphate, and concentrated under reduced pressure till dryness. The resulting crude product (5.2 g) was carried over to the next step without purification. by reflux for 6 h The progress of reaction After completion of reaction the reaction mixture was cooled to 0-10° C. washed with tetrahydrofuran (500 ml) The combined filtrate was concentrated under reduced pressure Water (100 ml) was added the aq. phase was extracted with ethyl acetate (3×100 ml) The combined organic layer was washed with brine (50 ml) dried over sodium sulphate concentrated under reduced pressure till dryness The resulting crude product (5.2 g) was carried over to the next step without purification

反応条件: temp:12.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 3,3-dimethylpiperazin-2-one (prepared according to procedure reported in WO200516900 A1, 6.0 g, 46.8 mmol) in N,N-dimethylformamide (10 ml) was added benzyl bromide (6.68 ml, 56.2 mmol) at 0° C., followed by addition of triethylamine (19.57 ml, 140 mmol). Reaction was stirred for 3 h at 0-25° C. The progress of reaction was monitored by TLC. After completion of reaction, the reaction mixture was diluted with ethyl acetate (100 ml) and water (100 ml). Aqueous layer was extracted with ethyl acetate (50 ml×6). The combined organic phase was washed with brine (50 mL) and dried over sodium sulphate and concentrated under reduced pressure till dryness. Crude compound was adsorbed on 100-200 mesh silica gel and purified by using flash column chromatography method using 5% methanol in dichloromethane as eluent. Title compound was eluted at 5% methanol in dichloromethane (6.2 g, 60.7%). Reaction The progress of reaction After completion of reaction Aqueous layer was extracted with ethyl acetate (50 ml×6) The combined organic phase was washed with brine (50 mL) dried over sodium sulphate concentrated under reduced pressure till dryness purified Title compound was eluted at 5% methanol in dichloromethane (6.2 g, 60.7%)