反应详情

温度

-78 °C

To a solution of 3-(methoxy-methyl-carbamoyl)-azetidine-1-carboxylic acid tert-butyl ester (6.0 g, 24.56 mmol) in THF (15 mL) at −78° C. was added a solution of methymagnesium bromide (3M in toluene, 12.3 mL, 36.9 mmol). The reaction mixture was stirred at −78° C. for 1 h. The reaction mixture was warmed to ambient temperature gradually and stirred for 1 h. The reaction was quenched by the addition of aqueous KHSO4 solution (20 mL). The aqueous layer was extracted with EtOAc (3×20 mL). The combined organic layers were washed with water (20 mL) and brine (20 mL), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 10% EtOAc in petroleum ether) to give 3-acetyl-azetidine-1-carboxylic acid tert-butyl ester (3.2 g, 65.4%). 1H NMR (DMSO-d6, 400 MHz): δ 3.88 (m, 4H), 3.53 (m, 1H), 2.08 (s, 3H), 1.34 (s, 9H).

1. temperatureThe reaction mixture was warmed to ambient temperature gradually
2. stirringstirred for 1 h
3. customThe reaction was quenched by the addition of aqueous KHSO4 solution (20 mL)
4. extractionThe aqueous layer was extracted with EtOAc (3×20 mL)
5. washThe combined organic layers were washed with water (20 mL) and brine (20 mL)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe residue was purified by column chromatography on silica gel (eluting with 10% EtOAc in petroleum ether)