反应详情

温度

85 °C

To a solution of 1.7 g of methyl 2-chloro-5-fluoro-6-(pyrrolidin-1-yl)nicotinate in 15 mL of N,N-dimethylformamide, 0.38 g of tetrakis(triphenylphosphine)palladium(0) and 1.4 mL of triethylamine were added at room temperature, and 0.37 mL of formic acid was dropped thereto. The mixture was stirred at 80 to 90° C. for 2 hours 30 minutes under a nitrogen atmosphere. After cooling to room temperature, water and ethyl acetate were added to the reaction mixture, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, and the resultant solution was washed with a saturated aqueous sodium chloride solution. To the organic layer, a mixed solvent of chloroform:methanol was added, the organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. To the resultant residue, a mixed solvent of diethyl ether:ethyl acetate (1:2) was added, the insoluble substance was filtered off, and the solvent was distilled off under reduced pressure. The resultant residue was purified by flash silica gel column chromatography using an eluent of chloroform to obtain 1.3 g of methyl 5-fluoro-6-(pyrrolidin-1-yl)nicotinate as a light yellow solid.

1. temperatureAfter cooling to room temperature
2. customthe organic layer was separated
3. extractionthe aqueous layer was extracted with ethyl acetate
4. washthe resultant solution was washed with a saturated aqueous sodium chloride solution
5. additionTo the organic layer, a mixed solvent of chloroform:methanol was added
6. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
7. distillationthe solvent was distilled off under reduced pressure
8. additionTo the resultant residue, a mixed solvent of diethyl ether:ethyl acetate (1:2) was added
9. filtrationthe insoluble substance was filtered off
10. distillationthe solvent was distilled off under reduced pressure
11. customThe resultant residue was purified by flash silica gel column chromatography