反应详情

To a solution of (+)-methyl 2-(4-bromo-2-fluorophenyl)cyclopropanecarboxylate from step 8 (1.2 eq) and boronate ester from step 4 (1 eq) in DMF-iPrOH (1:1, 0.1M), was added tris(dibenzylideneacetone)dipalladium(0) (0.055 eq), 2-(dimethylamino)-2′-(dicyclohexylphosphino)biphenyl (0.13 eq) and a sodium carbonate solution (2M, 4 eq) The reaction mixture was heated at 78° C. for 2 h. The reaction mixture was filtered on Celite and silica gel (1:1) and washed with EtOAc. The filtrate was concentrated in vacuo and remaining solvents were distilled in vacuo. The resulting yellow solid is stirred vigourously in ether. The residue then isolated by filtration and washed with ether. Mother liquors were further purified by flash chromatography (toluene/EtOAc, 100:0 to 70:30).

1. filtrationThe reaction mixture was filtered on Celite and silica gel (1:1)
2. washwashed with EtOAc
3. concentrationThe filtrate was concentrated in vacuo
4. distillationwere distilled in vacuo
5. customThe residue then isolated by filtration
6. washwashed with ether
7. customMother liquors were further purified by flash chromatography (toluene/EtOAc, 100:0 to 70:30)