反应详情

温度

80 °C

To a stirred mixture of 1-(2-Chloro-6H,12H-5-oxa-11-aza-dibenzo[a,e]cycloocten-11-yl)-ethanone Example 348D (21.5 mg, 74.7 umol), KF (14.3 mg, 0.25 mmol), phenylboranic acid (10.0 mg, 82.2 umol) and tri-t-butyl phosphine (4.54 mg, 22.4 umol) in dioxane (0.40 mL) under argon was added Pd2(dba)3 (6.84 mg, 7.47 umol). This mixture was heated at 80° C. for 19 hours and cooled to room temperature. To this cooled mixture under argon was added more Pd2 (dba)3 and tri-t-butyl phosphine. This mixture was then heated at 100° C. for 24 h upon which time some more Pd2 (dba)3 and tri-t-butyl phosphine were added. The mixture was heated at 80° C. for another 24 h and cooled to room temperature. This mixture was concentrated in vacuo and purified by a ISCO auto CombiFlash with a RediSep 4 g column, eluted with CH2Cl2-EtOAc, detected at 220 nM to give 4.3 mg of impure 1-(2-Phenyl-6H,12H-5-oxa-11-aza-dibenzo[a,e]cycloocten-11-yl)-ethanone Example 348. This was further purified by a Shimadzu auto prep HPLC, employing 30% to 100% 10 min gradient elution with 0.1% TFA in MeOH-water solvent system, 220 nM detection, 20 mL/min elution with a YMC ODS S5 20×100 mm column to give 3.3 mg of 1-(2-Phenyl-6H,12H-5-oxa-11-aza-dibenzo[a,e]cycloocten-11-yl)-ethanone Example 348 in 13% yield. HPLC Rt=3.53 min (YMC S5 ODS column 4.6×50 mm, 10-90% aqueous methanol over 4 minutes containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm) LC/MS: M+H=330

1. temperaturecooled to room temperature
2. additionwere added
3. temperatureThe mixture was heated at 80° C. for another 24 h
4. temperaturecooled to room temperature
5. concentrationThis mixture was concentrated in vacuo
6. custompurified by a ISCO auto CombiFlash with a RediSep 4 g column
7. washeluted with CH2Cl2-EtOAc