(S)-METHYL AZETIDINE-2-CARBOXYLATE

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (2S)-Methyl azetidine-2-carboxylate (2.83 g, 18.7 mmol, 1.0 eq) was dissolved in dry dichloromethane (100 mL) and cooled to about 0° C. under an argon atmosphere. After the addition of benzyl chloroformate (3.00 mL, 20.0 mmol, 1.1 eq), diisopropyl ethylamine (8.00 mL, 45.9 mmol, 2.5 eq) was added to the mixture dropwise. The reaction mixture was stirred at about 0° C. for about 30 minutes and then at about room temperature overnight. The solvent was evaporated and then the residue was dissolved in ether, washed with 1N HCl, water and brine, dried over magnesium sulfate and concentrated. Flash chromatography (in ether) gave 3.75 g (80% yield) of the product as a colorless oil. 1H NMR (CDCl3) δ 2.19-2.32 (m, 1H); 2.52-2.66 (m, 1H); 3.74 (s, 3H); 3.94-4.03 (m, 1H); 4.08-4.18 (m, 1H); 4.72 (dd, 1H, J=9.4, 6.9); 5.12 (q, 2H, J=12.9); 7.29-7.42 (m, 5H). was added to the mixture dropwise at about room temperature overnight The solvent was evaporated the residue was dissolved in ether washed with 1N HCl, water and brine dried over magnesium sulfate concentrated

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

实验步骤: To a mixture of the 1,5-dimethylpyrazole-3-carboxylic acid (433.1 mg, 3.09 mmol, 1.0 eq), diisopropylcarbodiimide (0.74 mL, 4.73 mmol, 1.5 eq), camphorsulfonic acid (300.6 mg, 1.29 mmol, 0.4 eq) and dimethylaminopyridine (129.7 mg, 1.06 mmol, 0.3 eq) in dry dichloromethane (30 mL) was added (2S)-methyl azetidine-2-carboxylate (474.4 mg, 3.13 mmol, 1.0 eq) in dry dichloromethane (12 mL) at about room temperature. The mixture was stirred at about room temperature for about 24 hours under argon. The solid was filtered off and washed with ether. The organic filtrate was concentrated and the residue subjected to flash chromatography (1-10% methanol in dichloromethane) to give 429.9 mg (58% yield) of the product. 1H NMR (CDCl3) δ 2.22-2.77 (series of s and m, 5H); 3.64-3.84 (series of s, 6H); 4.08-4.73 (series of m, 2H); 4.89 and 5.29 (dd, 1H, J=9.4, 6.0); 6.53 (s, 1H). The solid was filtered off washed with ether The organic filtrate was concentrated