反应详情

温度

90 °C

A mixture of methyl 6-fluoro-5-methylnicotinate (2.40 g, 14.2 mmol, Step-1 of Amine-36), 4-fluorophenol (2.39 g, 21.3 mmol), and potassium carbonate (3.92 g, 28.4 mmol) in DMF (45 mL) is stirred at 90° C. for 3 hours. After cooling to rt, the mixture is filtered through a pad of Celite and rinsed with EtOAc (200 mL). The filtrate is washed with water (200 mL) and brine (200 mL), and the organic layer is dried over sodium sulfate. After filtration, and the filtrate is concentrated in vacuo. The residue is purified by chromatography on silica gel eluting with n-hexane/EtOAc (20:1) to give 3.46 g (93% yield) of the title compound as white solid.

1. temperatureAfter cooling to rt
2. filtrationthe mixture is filtered through a pad of Celite
3. washrinsed with EtOAc (200 mL)
4. washThe filtrate is washed with water (200 mL) and brine (200 mL)
5. dry with materialthe organic layer is dried over sodium sulfate
6. filtrationAfter filtration
7. concentrationthe filtrate is concentrated in vacuo
8. customThe residue is purified by chromatography on silica gel eluting with n-hexane/EtOAc (20:1)