反应详情

温度

140 °C

In two microwave vials were placed 4-[(phenylmethyl)oxy]-1H-indole (500 mg, 2.24 mmoL), 4-bromo-2,5-difluorophenyl phenylmethyl ether (prepared as described in part a), 559 mg, 1.87 mmoL), K3PO4 (990 mg, 4.67 mmoL), L-Proline (43 mg, 0.373 mmoL) and DMF (5 mL) and the mixture was degassed by sonication under a flow of argon. To each vial was added CuI (71 mg, 0.373 mmoL) and the solutions were heated to 140° C. in the microwave reactor. After 4 hours a second portion of L-Proline (43 mg, 0.373 mmoL) was added and heated for an additional hour. The two mixtures were partitioned between ethyl acetate (100 mL)/water (100 mL), the phases were separated and the aqueous phase re-extracted with ethyl acetate (100 mL). The combined organic phases were washed with sat. NH4Cl (2×100 mL), water (100 mL) and brine (2×100 mL) and finally dried over MgSO4. The combined crude materials were purified by flash chromatography (Biotage SP4, 40+M Cartridge) eluting with a gradient of 0 to 30% Et2O in hexane to give the title compound (D22), (258 mg).

1. customprepared
2. customthe mixture was degassed by sonication under a flow of argon
3. additionTo each vial was added CuI (71 mg, 0.373 mmoL)
4. additionAfter 4 hours a second portion of L-Proline (43 mg, 0.373 mmoL) was added
5. temperatureheated for an additional hour
6. customThe two mixtures were partitioned between ethyl acetate (100 mL)/water (100 mL)
7. customthe phases were separated
8. extractionthe aqueous phase re-extracted with ethyl acetate (100 mL)
9. washThe combined organic phases were washed with sat. NH4Cl (2×100 mL), water (100 mL) and brine (2×100 mL)
10. dry with materialfinally dried over MgSO4
11. customwere purified by flash chromatography (Biotage SP4, 40+M Cartridge)
12. washeluting with a gradient of 0 to 30% Et2O in hexane