反应详情

温度

23 °C

Palladium(II) acetate (24 mg, 0.11 mmol, 0.020 equiv) was added to a vigourously stirred, deoxygenated mixture of tert-butyl 2,5-dihydro-1H-pyrrole-1-carboxylate (900 mg, 5.32 mmol) and 2-chloro-5-fluorobenzenediazonium tetrafluoroborate (1-1, 1.30 g, 5.32 mmol) in water and carbon tetrachloride (1:1, 50 mL) at 23° C., and the resulting mixture was stirred for 20 hours. The reaction mixture was partitioned between saturated aqueous sodium bicarbonate solution (150 mL) and ethyl acetate (2×150 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was dissolved in toluene (100 mL), and the resulting solution concentrated in vacuo to facilitate azeotropic removal of residual water. 2,6-Lutidine (1.24 mL, 10.6 mmol, 2.00 equiv) and trifluoroacetic anhydride (0.558 mL, 2.66 mmol, 0.500 equiv) were then sequentially added to a solution of the residue in toluene (100 mL) at 0° C. The resulting mixture was stirred at 0° C. for 8 hours, then warmed to 23° C. and stirred an additional 8 hours. The reaction mixture was heated at reflux for 1 hour, then cooled to 23° C. and concentrated. The residue was partitioned between ethyl acetate (100 mL) and saturated aqueous sodium bicarbonate solution (100 mL). The organic layer was dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (hexanes initially, grading to 60% EtOAc in hexanes) to give tert-butyl 3-(2-chloro-5-fluorophenyl)-2,3-dihydro-1H-pyrrole-1-carboxylate (1-2) as an orange oil. LRMS m/z (M+H—CH3) 283.0 found, 283.1 required.

1. customdeoxygenated
2. stirringthe resulting mixture was stirred for 20 hours
3. customThe reaction mixture was partitioned between saturated aqueous sodium bicarbonate solution (150 mL) and ethyl acetate (2×150 mL)
4. dry with materialThe combined organic layers were dried over sodium sulfate
5. concentrationconcentrated
6. dissolutionThe residue was dissolved in toluene (100 mL)
7. concentrationthe resulting solution concentrated in vacuo
8. customremoval of residual water
9. stirringThe resulting mixture was stirred at 0° C. for 8 hours
10. stirringstirred an additional 8 hours
11. temperatureThe reaction mixture was heated
12. temperatureat reflux for 1 hour
13. temperaturecooled to 23° C.
14. concentrationconcentrated
15. customThe residue was partitioned between ethyl acetate (100 mL) and saturated aqueous sodium bicarbonate solution (100 mL)
16. dry with materialThe organic layer was dried over sodium sulfate
17. concentrationconcentrated
18. customThe residue was purified by flash column chromatography (hexanes initially