反应详情

2-Chloro-pyrimidine-5-carboxylic acid 1 (3.16 g, 20 mmol) was suspended in dichloromethane (40 mL), and oxalyl chloride (3.30 g, 26 mmol) was added, followed by dimethylformamide (3 drops) as catalyst. The reaction started to vigorously evolve gas. The reaction was heated to reflux for 1 hour, then allowed to cool to room temperature. 4-fluoroaniline was added, vigorous bubbling was seen again, and the reaction mixture warmed up considerably. Triethylamine was added, and a flocculent precipitate immediately formed. The reaction mixture was heated to reflux once again for another hour, removed from heat, and stirred at room temperature for 18 hours under nitrogen. The reaction was diluted with ethyl acetate (100 mL), and the organic layer washed with water, saturated sodium bicarbonate, water, 1N HCl, water, saturated sodium chloride, then dried over sodium sulfate. The liquid was filtered, and evaporated to yield 3.44 g (68%) of compound 3 as a light yellow solid. ESI-MS m/z=252.0 [M+H]+.

1. temperatureThe reaction was heated
2. temperatureto reflux for 1 hour
3. customvigorous bubbling
4. temperaturethe reaction mixture warmed up considerably
5. additionTriethylamine was added
6. customa flocculent precipitate immediately formed
7. temperatureThe reaction mixture was heated
8. temperatureto reflux once again for another hour
9. customremoved
10. temperaturefrom heat
11. additionThe reaction was diluted with ethyl acetate (100 mL)
12. washthe organic layer washed with water, saturated sodium bicarbonate, water, 1N HCl, water, saturated sodium chloride
13. dry with materialdried over sodium sulfate
14. filtrationThe liquid was filtered
15. customevaporated