反应详情

温度

70 °C

Zinc (0.967 g, 14.8 mmol) was suspended with 1,2-dibromoethane (0.085 mL, 0.98 mmol) in DMF (17 mL). The mixture was heated at 70° C. for 10 min and then cooled to room temperature. Chlorotrimethylsilane (0.13 mL, 0.98 mmol) was added dropwise and stirring was continued for 1 hour. A solution of benzyl 3-iodoazetidine-1-carboxylate (3.9 g, 12 mmol, from Pharmablock) in DMF (10 mL) was then added and the mixture was heated at 40° C. for 1 h before a mixture of 1-(5-chloro-2-ethoxy-3-iodo-4-methylphenyl)ethanone (4.4 g, 13 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.22 g, 0.24 mmol) and tri-(2-furyl)phosphine (0.12 g, 0.50 mmol) in DMF (30 mL) was added. The reaction mixture was warmed to 70° C. and stirred overnight. The mixture was then cooled to room temperature and partitioned between ether and sat. NH4Cl solution. The organic layer was washed with water, dried over MgSO4, concentrated and purified on silica gel (eluting with 0 to 20% EtOAc in hexanes) to give the desired product (3.87 g, 78%). LCMS calculated for C22H25ClNO4 (M+H)+: m/z=402.1. found: 402.1.

1. temperaturecooled to room temperature
2. additionwas added
3. temperatureThe reaction mixture was warmed to 70° C.
4. stirringstirred overnight
5. temperatureThe mixture was then cooled to room temperature
6. custompartitioned between ether and sat. NH4Cl solution
7. washThe organic layer was washed with water
8. dry with materialdried over MgSO4
9. concentrationconcentrated
10. custompurified on silica gel (eluting with 0 to 20% EtOAc in hexanes)