反应详情

温度

130 °C

To a N-methylpyrrolidinone (20 mL) solution of 2-amino-6-chloro-nicotinic acid ethyl ester (2.00 g, 7.78 mmol) described in Manufacturing Example 170-1-1 were added tetramethyltin (1.62 mL, 11.7 mmol) and tetrakis(triphenylphosphine)palladium(0) (899 mg, 0.778 mmol), which was stirred under nitrogen atmosphere for 5 hours and 40 minutes at 130° C. Water was added to the reaction mixture at room temperature, which was extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered, and the filtrate was concentrated under a reduced pressure. The residue thus obtained was purified by NH silica gel column chromatography (heptane:ethyl acetate=3:1), and then further purified by silica gel column chromatography (heptane:ethyl acetate=2:1) to obtain the title compound (670 mg, 48%).

1. extractionwhich was extracted with ethyl acetate
2. washThe organic layer was washed with water and saturated aqueous sodium chloride
3. dry with materialdried over anhydrous magnesium sulfate
4. filtrationfiltered
5. concentrationthe filtrate was concentrated under a reduced pressure
6. customThe residue thus obtained
7. customwas purified by NH silica gel column chromatography (heptane:ethyl acetate=3:1)
8. customfurther purified by silica gel column chromatography (heptane:ethyl acetate=2:1)