反应详情

温度

60 °C

Zinc (1.71 g, 26.2 mmol) was suspended in N,N-dimethylformamide (45.0 mL) and 1,2-dibromoethane (210 μL, 2.5 mmol) was added. The mixture was heated at 60° C. for 10 minutes and then cooled to room temperature. Chlorotrimethylsilane (330 μL, 2.6 mmol) was added and stirred at 60° C. for 10 minutes and cooled to room temperature. A solution of tert-butyl 3-iodoazetidine-1-carboxylate (from Oakwood, 6.25 g, 22.1 mmol) in N,N-dimethylformamide (5.0 mL) was then added and the mixture stirred at room temperature for 1 hour. 1-(5-chloro-3-iodo-2-methoxy-4-methylphenyl)ethanone (5.00 g, 15.4 mmol), tri-(2-furyl)phosphine (358 mg, 1.54 mmol), and tris(dibenzylideneacetone)dipalladium(0) (0.70 g, 0.77 mmol) were added in order and the reaction mixture was warmed to 70° C. and stirred overnight. The mixture was cooled to room temperature and partitioned between ethyl acetate (EtOAc) and sat. NH4Cl solution. The layers were separated and the aqueous extracted further with EtOAc (2×). The combined organics were washed with water and brine, dried over MgSO4, and concentrated. The residue was purified on silica gel, eluting with 0-30% EtOAc in hexanes to give 3.0 g (55%) of the desired product as an orange solid. LCMS calculated for C18H24ClNO4Na (M+Na)+: m/z=376.1; Found: 376.0. 1H NMR (400 MHz, CDCl3): δ 7.52 (s, 1H), 4.32, (m, 2H), 4.16 (m, 3H), 3.66 (s, 3H), 2.59 (s, 3H), 2.31 (s, 3H), 1.45 (s, 9H) ppm.

1. temperaturecooled to room temperature
2. temperaturecooled to room temperature
3. stirringthe mixture stirred at room temperature for 1 hour
4. temperaturethe reaction mixture was warmed to 70° C.
5. stirringstirred overnight
6. temperatureThe mixture was cooled to room temperature
7. custompartitioned between ethyl acetate (EtOAc) and sat. NH4Cl solution
8. customThe layers were separated
9. extractionthe aqueous extracted further with EtOAc (2×)
10. washThe combined organics were washed with water and brine
11. dry with materialdried over MgSO4
12. concentrationconcentrated
13. customThe residue was purified on silica gel
14. washeluting with 0-30% EtOAc in hexanes