反应详情

A suspension of 22.4 g (129 mmol) of N-acetyl-L-4-hydroxyproline and 300 ml of dichloromethane is stirred at -10° and 18.06 ml (130 mmol) of triethylamine is added, followed by 10.2 ml (130 mmol) of methyl chloroformate at -10° to -15° C. The silylated acid solution from above is added in aliquots keeping the temperature below -5° C. When all is added, the reaction temperature is allowed to rise to 0° C. and the reaction flask is placed in an ice bath. The reaction is stirred overnight allowing the bath temperature to rise to room temperature. The reaction is filtered and filtrate is evaporated. Water is added to the residue and the mixture is stirred for 2 hrs and filtered. The product is resuspended in water, stirred, and filtered. The solid is taken up in isopropanol and a light precipitate is filtered off. The filtrate is evaporated down and the residue is washed with isopropanol and then ether. The product is suspended in water and cooled in an ice bath. The pH is adjusted to 2.15 with dilute hydrochloric acid and the precipitate is filtered. The solid is taken up in isopropanol and the insolubles filtered off. The solids are dissolved in methanol and added to the isopropanol solution. The resulting solution is evaporated down and ether added to the residue. A light yellow solid is obtained and dried under vacuum to give 8.8 g of 2-[4-acetyl-L-hydroxyprolylamino)phenyl]-4-hydroxy-5-pyrimidine carboxylic acid.

1. additionThe silylated acid solution from above is added in aliquots
2. customthe temperature below -5° C
3. additionWhen all is added
4. customto rise to 0° C.
5. customthe reaction flask is placed in an ice bath
6. stirringThe reaction is stirred overnight
7. customto rise to room temperature
8. filtrationThe reaction is filtered
9. customfiltrate is evaporated
10. additionWater is added to the residue
11. stirringthe mixture is stirred for 2 hrs
12. filtrationfiltered
13. stirringstirred
14. filtrationfiltered
15. filtrationa light precipitate is filtered off
16. customThe filtrate is evaporated down
17. washthe residue is washed with isopropanol
18. temperaturecooled in an ice bath
19. filtrationthe precipitate is filtered
20. filtrationthe insolubles filtered off
21. dissolutionThe solids are dissolved in methanol
22. additionadded to the isopropanol solution
23. customThe resulting solution is evaporated down
24. additionether added to the residue
25. customA light yellow solid is obtained
26. customdried under vacuum