反应详情

85.5 g of 2-methoxy-4-acetamino-5-ethylsulphinyl benzoic acid, 85 ml of water, 342 ml of acetone and 31 g of triethylamine are placed in a 1 liter flask fitted with an agitator, a thermometer and a dropping funnel. The mixture is agitated until the solids dissolve, then 32.5 g of ethyl chloroformate is added drop by drop while the temperature is kept at about 10° C. The reaction medium is agitated for 30 minutes at room temperature then cooled to 5°-10° C. and 50.4 g of 1-cyclopentyl-2-aminomethylpyrrolidine is added drop by drop in the course of 1 hour. Agitation is continued for 2 hours at room temperature, then the reaction mixture is evaporated to dryness under vacuum. The residue is dissolved in 300 ml of water and the suspension is extracted with 500 ml then twice with 300 ml of methylene chloride. The organic phase is washed twice with 200 ml of water and evaporated under vacuum. The oily residue is dissolved hot in 300 ml of water. 90 ml of soda lye is added and the medium is heated to reflux for 2 hours 30. An oil appears rapidly. It is cooled, the suspension is extracted twice with 250 ml methylene chloride, and the organic solution is washed three times with 200 ml of water. It is dried over magnesium sulphate, filtered and evaporated to dryness under vacuum. The residue is dissolved in 320 ml of ethyl acetate, then the product is left to crystallise in a refrigerator. The crystals are filtered off and dried in an oven at 50° C.

1. customfitted with an agitator
2. dissolutiondissolve
3. customis kept at about 10° C
4. stirringThe reaction medium is agitated for 30 minutes at room temperature
5. temperaturethen cooled to 5°-10° C.
6. customthe reaction mixture is evaporated to dryness under vacuum
7. dissolutionThe residue is dissolved in 300 ml of water
8. extractionthe suspension is extracted with 500 ml
9. washThe organic phase is washed twice with 200 ml of water
10. customevaporated under vacuum
11. dissolutionThe oily residue is dissolved hot in 300 ml of water
12. addition90 ml of soda lye is added
13. temperaturethe medium is heated
14. temperatureto reflux for 2 hours 30
15. temperatureIt is cooled
16. extractionthe suspension is extracted twice with 250 ml methylene chloride
17. washthe organic solution is washed three times with 200 ml of water
18. dry with materialIt is dried over magnesium sulphate
19. filtrationfiltered
20. customevaporated to dryness under vacuum
21. dissolutionThe residue is dissolved in 320 ml of ethyl acetate
22. waitthe product is left
23. customto crystallise in a refrigerator
24. filtrationThe crystals are filtered off
25. customdried in an oven at 50° C.