4-(2-氧代乙基)哌嗪-1-甲酸叔丁酯

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 1 M of potassium tert-butoxide in THF (45.5 mL, 0.0455 mol) at 0° C. was added drop wise a solution of diethyl cyanomethylphosphonate (7.72 mL, 0.0477 mol) in THF (70 mL). The reaction mixture was warmed up to at RT, cooled to 0° C. again, and a solution of tert-butyl 4-(2-oxoethyl)piperazine-1-carboxylate (9.90 g, 0.0434 mol) in THF (10 mL) was added. The reaction mixture was allowed to warm up to RT and stirred for 2 more hours. After being quenched with water, the mixture was extracted with EtOAc. The organic layers were dried and concentrated. The residue was purified by silica gel column eluting with DCM to give the desired product (7.5 g, 69%). cooled to 0° C. again to warm up to RT After being quenched with water the mixture was extracted with EtOAc The organic layers were dried concentrated The residue was purified by silica gel column eluting with DCM

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Oxalyl chloride (3.6 mL, 0.0425 mol) was dissolved in DCM (87 mL) at −78° C. Dimethyl sulfoxide (6.58 mL, 0.0927 mol) was added and the solution was held at −78° C. for 10 min. To the resultant mixture was added a solution of tert-butyl 4-(2-hydroxyethyl)piperazine-1-carboxylate (from Oakwood, 8.90 g, 0.0386 mol) in DCM (44 mL) over 15 min. The reaction was stirred at −78° C. for 1 h, then triethylamine (26.9 mL, 0.193 mol) was added. The mixture was warmed to RT over 30 minutes and then stirred at RT for another 30 min. The mixture was diluted with DCM, washed with water (2×), brine (1×), dried over sodium sulfate, and concentrated. The crude product (8.10 g, 91.8%) was used directly in next step without further purification. 1H NMR (400 MHz, CDCl3): δ 9.70 (1H, s), 3.48 (4H, m), 3.19 (2H, s), 2.47 (4H, m), 1.45 (9H, s) ppm. The mixture was warmed to RT over 30 minutes stirred at RT for another 30 min washed with water (2×), brine (1×) dried over sodium sulfate concentrated The crude product (8.10 g, 91.8%) was used directly in next step without further purification