반응 #69467
ord-6c347fd2053c4b53bdc6763a8606b949
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후처리
- 1기타was bubbled with nitrogen for 10 minutes
- 2기타the mixture bubbled with nitrogen for 2 minutes
- 3온도Upon cooling to room temperature the mixture
- 4기타was partitioned between DCM (500 mL) and water (250 mL)
- 5세척The organic phase was washed with brine
- 6건조dried with magnesium sulfate
- 7여과filtered
- 8농축concentrated under reduced pressure
- 9기타to give a brown gum
- 10기타The gum was purified by flash column chromatography on silica using gradient elution (0% methanol/DCM to 5% methanol/DCM)
실험 절차
6-(morpholine-4-carbonyl)-2-morpholino-8-(pyrrolidin-2-yl)-4H-chromen-4-one (296 g, 716 mmol), 1-bromo-3,5-difluorobenzene (173 g, 895 mmol) and cesium carbonate (700 g, 2148 mmol) suspended in dioxane (3 L) was bubbled with nitrogen for 10 minutes. diacetoxypalladium (8.04 g, 36 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (41.4 g, 72 mmol) were added and the mixture bubbled with nitrogen for 2 minutes then heated at 100° C. for 2 hours. Upon cooling to room temperature the mixture was partitioned between DCM (500 mL) and water (250 mL). The organic phase was washed with brine and dried with magnesium sulfate, filtered and concentrated under reduced pressure to give a brown gum. The gum was purified by flash column chromatography on silica using gradient elution (0% methanol/DCM to 5% methanol/DCM). The desired product, 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-6-(morpholine-4-carbonyl)-2-morpholino-4H-chromen-4-one (282 g, 75%), was thus isolated as a pale yellow dry film. Mass Spectrum: m/z [M+H]+=526. More material was made by repeating this reaction.