반응 #69497

반응 방정식

methyl 2-((R)-2-methylmorpholino)-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate

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

1-bromo-3,5-difluorobenzene

cesium carbonate

→

methyl 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-((R)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxylate

수율 61.0%

용매

1,4-dioxane

반응 조건

후처리

1. 1
   기타The resulting suspension was degassed with argon
2. 2
   온도to cool to room temperature
3. 3
   기타the insoluble were removed by filtration
4. 4
   농축the filtrate concentrated
5. 5
   기타purified by flash chromatography on silica gel eluting with 0 to 6% MeOH in EtAc
6. 6
   기타The solvent was evaporated to dryness

실험 절차

Diacetoxypalladium (4.58 mg, 0.02 mmol) was added to a stirred mixture of methyl 2-((R)-2-methylmorpholino)-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (190 mg, 0.51 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (25.09 mg, 0.04 mmol), 1-bromo-3,5-difluorobenzene (73.4 μl, 0.64 mmol) and cesium carbonate (249 mg, 0.77 mmol) suspended in 1,4-dioxane (5 mL). The resulting suspension was degassed with argon and then stirred at 100° C. for 20 h. The reaction mixture was allowed to cool to room temperature, the insoluble were removed by filtration and the filtrate concentrated. The crude product was adsorbed on silica gel and purified by flash chromatography on silica gel eluting with 0 to 6% MeOH in EtAc. The solvent was evaporated to dryness to afford methyl 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-((R)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxylate (150 mg, 61%) as a beige foam.

출처