反应详情

温度

70 °C

Zinc dust (253 mg) was stirred under nitrogen overnight. To this was added DMF (5 ml) and dibromomethane (55 mg) dissolved in DMF (1 ml) and the mixture warmed to ˜70° C. The reaction mixture was cooled to room temperature and chlorotrimethylsilane (32 mg) in DMF (1 ml) added and stirred at room temperature for 15 minutes. To this was added 2-iodo-N-Boc-azetidine (Billotte, S., Synlett, 1998, 379-380) (1.04 g) in DMF (5 ml). The reaction mixture warmed to 40° C. and the mixture sonicated for 30 minutes during which time the zinc powder dissolved to leave a hazy solution. To the solution of zincate was added 4-iodobenzaldehyde (Preparation 43) (851 mg in 5 ml DMF), tri-2-furylphosphine (35 mg in 1 ml DMF) and Pd(dbq)2 (42 ml in 1 ml DMF). The resulting mixture was heated at 60-70° C. for 4 hours, cooled to room temperature and partitioned between ammonium chloride solution and diethyl ether, and the aqueous layer was extracted with diethyl ether (3×). The combined organic extracts were dried (Na2SO4), evaporated in vacuo and purified over silica (pentane:ethyl acetate; 4:1) to afford the title compound as a mobile oil, 626 mg.

1. temperatureThe reaction mixture was cooled to room temperature
2. temperatureThe reaction mixture warmed to 40° C.
3. dissolutiondissolved
4. customto leave a hazy solution
5. temperatureThe resulting mixture was heated at 60-70° C. for 4 hours
6. temperaturecooled to room temperature
7. custompartitioned between ammonium chloride solution and diethyl ether
8. extractionthe aqueous layer was extracted with diethyl ether (3×)
9. dry with materialThe combined organic extracts were dried (Na2SO4)
10. customevaporated in vacuo
11. custompurified over silica (pentane:ethyl acetate; 4:1)