反应详情

4-[(2-Chloro-5-fluoro-pyridine-3-carbonyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester (4.0 g, 11.18 mmol) (see Preparation 27), 4-fluorophenol (1.378 g, 12.3 mmol) and caesium carbonate (7.29 g, 33.54 mmol) were stirred in N,N-dimethylformamide (40 ml) at 55° C. under an atmosphere of nitrogen for 18 hours. The reaction mixture was then partitioned between ethyl acetate (50 ml) and water (30 ml) and the organic layer separated. The organic layer was then washed with a saturated aqueous solution of sodium chloride (40 ml), dried over anhydrous magnesium sulphate and the solvent removed in vacuo. The residue was purified by flash column chromatography on silica gel eluting with dichloromethane. The product was finally triturated with diethylether (25 ml) giving 4-{[5-fluoro-2-(4-fluorophenoxy)-pyridine-3-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester (2.59 g) as a white solid.

1. customThe reaction mixture was then partitioned between ethyl acetate (50 ml) and water (30 ml)
2. customthe organic layer separated
3. washThe organic layer was then washed with a saturated aqueous solution of sodium chloride (40 ml)
4. dry with materialdried over anhydrous magnesium sulphate
5. customthe solvent removed in vacuo
6. customThe residue was purified by flash column chromatography on silica gel eluting with dichloromethane
7. customThe product was finally triturated with diethylether (25 ml)