反应详情

温度

0 °C

To a solution of tert-butyl (3-bromo-2-chloro-5-cyanophenyl)(4-methoxybenzyl)carbamate (Intermediate (500 mg, 1.107 mmol) in THF (2.5 ml) at 0° C. was added drop wise isopropylmagnesium lithium chloride (1.3 M in THF) (0.937 mL, 1.218 mmol) under nitrogen. After stirring at 0° C. for 30 min, removal of the cooling bath and stirred at room temperature for 30 min. The reaction mixture was cooled to −14° C. (NaCl-ice bath), to this was added drop wise a solution of tert-butyl 3-oxoazetidine-1-carboxylate (208 mg, 1.218 mmol) in THF (2 mL), and left stirring in the cooling bath for 2 h, during this time the temperature rose to −4° C. The reaction was quenched with sat, aqueous NH4Cl solution (5 ml), and diluted with EtOAc, washed with water, brine, and dried over Na2SO4. Solvent was removed. The crude residue was purified by ISCO (12 g) column chromatography, eluting with hexane containing 0 to 40% EtOAc to afford tert-butyl 3-(3-((tert-butoxycarbonyl)(4-methoxybenzyl)amino)-2-chloro-5-cyanophenyl)-3-hydroxyazetidine-1-carboxylate (408 mg).

1. customremoval of the cooling bath
2. stirringstirred at room temperature for 30 min
3. temperatureThe reaction mixture was cooled to −14° C. (NaCl-ice bath)
4. waitleft
5. stirringstirring in the cooling bath for 2 h, during this time the temperature
6. customrose to −4° C
7. customThe reaction was quenched
8. additionaqueous NH4Cl solution (5 ml), and diluted with EtOAc
9. washwashed with water, brine
10. dry with materialdried over Na2SO4
11. customSolvent was removed
12. customThe crude residue was purified by ISCO (12 g) column chromatography
13. washeluting with hexane containing 0 to 40% EtOAc