反应详情

温度

35 °C

Phenyl lithium (12.9 mL, 23.3 mmol, 1.8 M solution in dibutyl ether) was provided in argon and mixed in drops with a solution of the title compound from step 3 (2.23 g, 7.76 mmol) in abs. diethyl ether (30 mL) at RT. During this, the reaction solution heated to 35° C. and a solid separated out. The reaction mixture was stirred for 1 h with reflux (bath 50° C.), then hydrolysed in the ice bath (0-10° C.) with 20% NH4Cl solution (20 mL) and the organic phase was separated. The aqueous phase was extracted with ether (3×50 mL). The combined organic solutions were dried over Na2SO4 and concentrated to low volume in a vacuum. By means of flash chromatography (100 g silica gel) with ethyl acetate/methanol (20:1→9:1→MeOH→MeOH+2% NH3) the non-polar diastereoisomer was obtained in a mixed fraction with starting substance and ketone and lastly the polar diastereoisomer. The mixed fraction with non-polar diastereoisomer was purified again by flash chromatography with dichloromethane/methanol (50:1→20:1→9:1→4:1).

1. customat RT
2. customa solid separated out
3. temperaturewith reflux (bath 50° C.)
4. customhydrolysed in the ice bath (0-10° C.) with 20% NH4Cl solution (20 mL) and the organic phase was separated
5. extractionThe aqueous phase was extracted with ether (3×50 mL)
6. dry with materialThe combined organic solutions were dried over Na2SO4
7. concentrationconcentrated to low volume in a vacuum
8. customBy means of flash chromatography (100 g silica gel) with ethyl acetate/methanol (20:1→9:1→MeOH→MeOH+2% NH3) the non-polar diastereoisomer was obtained in a mixed fraction
9. customThe mixed fraction with non-polar diastereoisomer was purified again by flash chromatography with dichloromethane/methanol (50:1→20:1→9:1→4:1)