反应详情

温度

100 °C

A mixture of 4-chloro-2-(1-(5-methyl-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-1-one (540 mg, 1.40 mmol, Intermediate-2, single enantiomer), palladium(II) acetate (190 mg, 0.84 mmol), 1,3-bis(diphenylphosphino)propane (115 mg, 0.28 mmol), and triethylamine (0.58 mL, 4.20 mmol) in DMF/MeOH (2.5:1, 14 mL) is heated at 100° C. under carbon monoxide atmosphere for 18 hours. The reaction mixture is cooled to rt and dilute with water. The mixture is filtered through a pad of Celite™ and the filtrate is extracted with n-hexane/EtOAc (1:1) mixed solvent. The combined extracts are washed with water, and brine. The organic extract is dried over sodium sulfate, filtrate, and volatiles are removed. The residue is purified by column chromatography on silica gel eluting with n-hexane/EtOAc (1:1 to 1:4) to give 300 mg (52% yield) of the title compound as brown amorphous solid.

1. temperatureThe reaction mixture is cooled to rt
2. filtrationThe mixture is filtered through a pad of Celite™
3. extractionthe filtrate is extracted with n-hexane/EtOAc (1:1)
4. additionmixed solvent
5. washThe combined extracts are washed with water, and brine
6. extractionThe organic extract
7. dry with materialis dried over sodium sulfate, filtrate, and volatiles
8. customare removed
9. customThe residue is purified by column chromatography on silica gel eluting with n-hexane/EtOAc (1:1 to 1:4)