反应详情

温度

15 °C

To a suspension of 29.6 g of 60% sodium hydride (0.74 mole) in 300 ml of tetrahydrofuran under a nitrogen blanket and at reflux was added dropwise at a rate to maintain good reflux a solution of 74.5 g (0.36 mole) of 2,5-dichloro-6-methyl-3-pyridinecarboxylic acid and 36.5 g (0.36 mole) of N-methylpyrrolidinol in 300 ml of tetrahydrofuran. The mixture was heated at reflux for 2 hr and cooled to 15° C. To the mixture was added dropwise, carefully, 47.2 g of oxalyl chloride between 15°-20° C. The mixture was stirred at room temperature for 1.5 hr followed by addition of 400 ml of water. Stirring was continued for 10 minutes. Tetrahydrofuran was removed by rotary evaporation and the remaining aqueous extracted with 3×200 ml of toluene. The combined organic layers were washed with 300 ml of water, dried over sodium sulfate, filtered, charcoaled, and concentrated by rotary evaporation. The residue was crystallized from isopropyl alcohol/isopropyl ether to give 33 g (30%) of crystals. A 3 g sample was recrystallized from isopropyl ether to give an analytically pure sample, m.p. 65°-69° C.

1. temperatureat reflux
2. additionwas added dropwise at a rate
3. temperatureto maintain good
4. temperatureThe mixture was heated
5. temperatureat reflux for 2 hr
6. additionTo the mixture was added dropwise
7. custombetween 15°-20° C
8. stirringStirring
9. waitwas continued for 10 minutes
10. customTetrahydrofuran was removed by rotary evaporation
11. extractionthe remaining aqueous extracted with 3×200 ml of toluene
12. washThe combined organic layers were washed with 300 ml of water
13. dry with materialdried over sodium sulfate
14. filtrationfiltered
15. concentrationconcentrated by rotary evaporation
16. customThe residue was crystallized from isopropyl alcohol/isopropyl ether