反应详情

A suspension of trimethylacetamide (18.08 g, 178.744 mmol), Cs2CO3 (68.823 g, 211.242 mmol), Pd2(dba)3 (1.488 g, 1.625 mmol) and Xantphos (4,5-bis-(diphenylphosphino)-9,9-dimethylxanthene) (1.880 g, 3.249 mmol) in dry, degassed 1,4-dioxane (800 ml) under argon was sonicated for 0.25 h and then treated with 2-chloro-6-(methyloxy)pyridine (19.32 ml, 162.494 mmol). The mixture was then heated at reflux for 24 h. The mixture was evaporated, treated with water (1 L) and extracted 3×DCM (1 L and then 2×500 ml). The organic extracts were dried (MgSO4), evaporated and chromatographed (50-100% DCM/40-60 Petroleum ether then 0-5% methanol/DCM) to give title compound as a yellow solid (25.191 g, 121.111 mmol, 75%). Impure fractions were recolumed (eluting as above) to give more product (4.990 g, 23.990 mmol, 15%). Total yield of 90%.

1. customin dry
2. customdegassed 1,4-dioxane (800 ml) under argon
3. customwas sonicated for 0.25 h
4. temperatureThe mixture was then heated
5. temperatureat reflux for 24 h
6. customThe mixture was evaporated
7. additiontreated with water (1 L)
8. extractionextracted 3×DCM (1 L
9. dry with materialThe organic extracts were dried (MgSO4)
10. customevaporated
11. customchromatographed (50-100% DCM/40-60 Petroleum ether