反应详情

Under an atmosphere of argon, 3-bromo-2-methyl-indolizine-6-carbonitrile (500 mg, 2.12 mmol), Pd2(dba)3 (19.5 mg, 21.2 μmol, 0.01 equiv), 1,2,3,4,5-pentaphenyl-1-(di-tert-butylphosphino)ferrocene (15.1 mg, 21.2 1μmol, 0.01 equiv) and the isolated, recrystallized Reformatsky reagent prepared from tert-butyl bromoacetate (609 mg, 2.33 mmol, 1.1 equiv) are placed in a 50-ml round bottom flask. After three careful degassing cycles, anhydrous THF (8 ml) is added, and the reaction mixture is stirred at room temperature. After 1 hour at room temperature, TLC analysis indicated incomplete conversion. Consequently, additional portions of the palladium salt, the phosphino ligand and the Reformatsky reagent are added (same quantities as above). After 1 additional hour, reagents are added again, to achieve complete conversion after a total reaction time of 4 hours at room temperature. The reaction mixture is diluted with water, and extracted three times with EtOAc. The combined organic layers are washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. Purification of the residue via flash chromatography (hexane/EtOAc 6:1) affords the title compound (390 mg, 68%). 1H NMR (400 MHz, CDCl3): δ=8.22 (t, J=1.2 Hz, 1H), 7.36 (d, J=9.2 Hz, 1H), 7.21 (s, 1H), 6.67 (dd, J=9.3/1.5 Hz, 1H). 3.61 (s, 2H), 2.31 (s, 3H), 1.44 (s, 9H). MS (ES+): 271 (M+H)+.

1. customare placed in a 50-ml round bottom flask
2. customAfter three careful degassing cycles, anhydrous THF (8 ml)
3. additionis added
4. additionConsequently, additional portions of the palladium salt, the phosphino ligand and the Reformatsky reagent are added (same quantities as above)
5. additionAfter 1 additional hour, reagents are added again
6. customafter a total reaction time of 4 hours
7. customat room temperature
8. additionThe reaction mixture is diluted with water
9. extractionextracted three times with EtOAc
10. washThe combined organic layers are washed with brine
11. dry with materialdried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated in vacuo
14. customPurification of the residue via flash chromatography (hexane/EtOAc 6:1)