تفاعل #69497

معادلة التفاعل

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

المردود 61.0%

المذيبات

1,4-dioxane

ظروف التفاعل

المعالجة

1. 1
   أخرىThe resulting suspension was degassed with argon
2. 2
   درجة الحرارةto cool to room temperature
3. 3
   أخرىthe insoluble were removed by filtration
4. 4
   تركيزthe filtrate concentrated
5. 5
   أخرىpurified by flash chromatography on silica gel eluting with 0 to 6% MeOH in EtAc
6. 6
   أخرىThe solvent was evaporated to dryness

الإجراء التجريبي

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.

المصدر