Reaktion #69467

Reaktionsgleichung

cesium carbonate

6-(morpholine-4-carbonyl)-2-morpholino-8-(pyrrolidin-2-yl)-4H-chromen-4-one

(9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine)

1-bromo-3,5-difluorobenzene

→

desired product

8-[(2R)-1-(3,5-difluorophenyl)pyrrolidin-2-yl]-6-(morpholine-4-carbonyl)-2-morpholino-chromen-4-one

8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-6-(morpholine-4-carbonyl)-2-morpholino-4H-chromen-4-one

Ausbeute 149.9%

Lösungsmittel

dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigewas bubbled with nitrogen for 10 minutes
2. 2
   Sonstigethe mixture bubbled with nitrogen for 2 minutes
3. 3
   TemperaturUpon cooling to room temperature the mixture
4. 4
   Sonstigewas partitioned between DCM (500 mL) and water (250 mL)
5. 5
   WaschenThe organic phase was washed with brine
6. 6
   Trocknendried with magnesium sulfate
7. 7
   Filtrationfiltered
8. 8
   Einengenconcentrated under reduced pressure
9. 9
   Sonstigeto give a brown gum
10. 10
    SonstigeThe gum was purified by flash column chromatography on silica using gradient elution (0% methanol/DCM to 5% methanol/DCM)

Vorschrift

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.

Quelle