tert-butyl (2S)-2-(2-cyanoacetyl)pyrrolidine-1-carboxylate

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: tert-Butyl (2S)-2-(2-cyanoacetyl)pyrrolidine-1-carboxylate (5.8 g, 24.3 mmol), was dissolved in EtOH (100 mL). Methylhydrazine (1.8 mL, 35 mmol) was added and the resulting mixture was heated, for about 12 h, at about 80° C. After cooling to rt, the mixture was concentrated in vacuo. The residue was taken up in toluene (50 mL) and stirred overnight. The precipitated solid was collected by filtration and washed with toluene (2 mL) and diethyl ether to afford tert-butyl (2S)-2-(5-amino-1-methyl-pyrazol-3-yl)pyrrolidine-1-carboxylate (4.43 g, 16.3 mmol, 68%), as white solid: 1H-NMR (CDCl3, Bruker 400 MHz, rotamers) δ 1.35 and 1.45 (9 H, br. s), 1.70-2.24 (4 H, m), 3.36-3.53 (4 H, m), 3.60 (3 H, br s), 4.70-4.78 and 4.83-4.90 (1 H, m), 5.35 and 5.41 (1H, br s). After cooling to rt the mixture was concentrated in vacuo The precipitated solid was collected by filtration washed with toluene (2 mL) and diethyl ether

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

实验步骤: To a solution of acetonitrile (1.5 mL, 29 mmol) in THF (60 mL) was added n-butyl lithium (2.5 M solution in hexane, 10.8 mL, 29 mmol) at −78° C. The solution was stirred at about −78° C. for about 10 min and a solution of 1-tert-butyl 2-methyl (2S)-pyrrolidine-1,2-dicarboxylate (5.64 g, 25 mmol, US2007197506) in 15 mL of THF was added. The mixture was stirred at about −78° C. for about 1 hr and was subsequently allowed to reach rt (overnight). Water was added and the mixture acidified to pH 3 with 1N aqueous hydrochloric acid. The layers were separated and the organic layer was washed with water (10 mL) and brine (10 mL), dried (MgSO4), filtered and concentrated in vacuo to give tert-butyl (2S)-2-(2-cyanoacetyl)pyrrolidine-1-carboxylate (5.8 g, 24.3 mmol, 97%) as a yellow oil. The mixture was stirred at about −78° C. for about 1 hr to reach rt (overnight) The layers were separated the organic layer was washed with water (10 mL) and brine (10 mL) dried (MgSO4) filtered concentrated in vacuo