反应详情

A mixture of 5-methyl-6-(2,2,2-trifluoroethoxy)nicotinic acid (3.08 g, 13.1 mmol, Step-1 of Amine-2), iodomethane (0.983 ml, 15.72 mmol) and potassium carbonate (5.43 g, 39.3 mmol) in DMA (40 ml) is stirred at rt for 2 hours. The reaction mixture is poured into water (200 mL) and extracted with n-hexane/EtOAc (1:10, 500 mL). The organic layer is washed with 2M hydrochloric acid (300 mL×2) and dried over sodium sulfate. After filtration, the filtrate is concentrated in vacuo. The residue is purified by column chromatography on silica gel eluting with n-hexane/EtOAc (5:1) to give 2.87 g (88% yield) of the title compound as white solid.

1. extractionextracted with n-hexane/EtOAc (1:10, 500 mL)
2. washThe organic layer is washed with 2M hydrochloric acid (300 mL×2)
3. dry with materialdried over sodium sulfate
4. filtrationAfter filtration
5. concentrationthe filtrate is concentrated in vacuo
6. customThe residue is purified by column chromatography on silica gel eluting with n-hexane/EtOAc (5:1)