N-methylpiperazine-1-carboxamide;hydrochloride

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

実験手順: To a suspension of N-methylpiperazine-1-carboxamide hydrochloride (6 g, 33.52 mmol) and K2CO3 (9.26 g, 67.0 mmol) in acetonitrile (100 mL) was added bromopropionic acid tert-butyl ester (8.4 g, 40.2 mmol). The reaction mixture was stirred at reflux for 12 h, cooled to room temperature and partitioned in ethyl acetate (200 mL) and water (100 mL). Organic layer was separated, dried (MgSO4), and concentrated to give tert-butyl 3-(4-(methylcarbamoyl)piperazin-1-yl)propanoate as an oil which was dissolved in a mixture of dichloromethane (100 mL) and TFA (trifluoroacetic acid) (20 mL) and then stirred overnight. The volatiles were removed under vacuum. The residue was dissolved in methanol, 1N hydrogen chloride in ether was added, and then the solution was concentrated to give 3-(4-(methylcarbamoyl)piperazin-1-yl)propanoic acid as a solid. LCMS 216 (M+1) at reflux for 12 h partitioned in ethyl acetate (200 mL) Organic layer was separated dried (MgSO4) concentrated

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

実験手順: To a suspension of N-methylpiperazine-1-carboxamide hydrochloride (6 g, 33.52 mmol) and K2CO3 (9.26 g, 67.0 mmol) in acetonitrile (100 mL) was added bromopropionic acid tert-butyl ester (8.4 g, 40.2 mmol). The reaction mixture was stirred at reflux for 12 h, cooled to room temperature and partitioned in ethyl acetate (200 mL) and water (100 mL). Organic layer was separated, dried (MgSO4), and concentrated to give tert-butyl 3-(4-(methylcarbamoyl)piperazin-1-yl)propanoate as an oil which was dissolved in a mixture of dichloromethane (100 mL) and TFA (trifluoroacetic acid) (20 mL) and then stirred overnight. The volatiles were removed under vacuum. The residue was dissolved in methanol, 1N hydrogen chloride in ether was added, and then the solution was concentrated to give 3-(4-(methylcarbamoyl)piperazin-1-yl)propanoic acid as a solid. LCMS 216 (M+1) at reflux for 12 h partitioned in ethyl acetate (200 mL) Organic layer was separated dried (MgSO4) concentrated