Dicyclohexylcarbodiimide → Acetamide, N-(2-(2-formyl-1-pyrrolidinyl)-2-oxoethyl)-, (S)-

Temperature

4 °C

In 150 ml of THF was dissolved 11.7 g of acetyl-glycin. To this solution were added 11.5 g of HOSu and 20.6 g of DCC, and the mixture was stirred for 21 hours at 4° C. The reaction liquid was filtered and the filtrate was evaporated under reduced pressure whereby a semi-solid substance was obtained. This substance was recrystallized from chloroform to obtain a white solid substance which was then dissolved in 350 ml of THF. To this solution was added 4.2 g of L-prolinol, and the mixture was stirred for 72 hours at room temperature. After removal of THF by distillation, the residue was dissolved in 200 ml of ethyl acetate and the solution was washed with 100 ml of 1-M Na2CO3, dehydrated with anhydrous Na2SO4 and evaporated until dryness. To the resultant oily substance were added 18.6 g of WSCD.HCl and 75 ml of redistilled DMSO, and the mixture was stirred for 10 minutes. Subsequently, 3.2 ml of a DMSO solution of 2-M anhydrous H3PO4 was added and the mixture was stirred for further 2 hours. The reaction was stopped with 160 ml of a buffer solution of 1-M potassium phosphate of pH 7.5. The reaction mixture was extracted with 150 ml of ethyl acetate, and the extract was dried over anhydrous Na2SO4. The ethyl acetate was distilled off and the residue was dissolved in 100 ml of ethanol. To this solution was added 50 g of NaHOS3 in 90 ml of water, and the mixture was stirred vigorously for 10 minutes. After concentration of the ethanol up to about 90 ml, unreacted materials were eliminated twice with 60 ml of ether, and solid Na2CO3 was added until the pH value of the liquid became 9. After 5 minutes, the reaction liquid was extracted twice with 60 ml of ether, and the ether was then distilled off to leave an oily substance. Yield 0.3 g (1.5%).

1. customThe reaction liquid
2. filtrationwas filtered
3. customthe filtrate was evaporated under reduced pressure whereby a semi-solid substance
4. customwas obtained
5. customThis substance was recrystallized from chloroform
6. customto obtain a white solid substance which
7. stirringthe mixture was stirred for 72 hours at room temperature
8. customAfter removal of THF
9. distillationby distillation
10. dissolutionthe residue was dissolved in 200 ml of ethyl acetate
11. washthe solution was washed with 100 ml of 1-M Na2CO3
12. customevaporated until dryness
13. additionTo the resultant oily substance were added 18.6 g of WSCD
14. stirringHCl and 75 ml of redistilled DMSO, and the mixture was stirred for 10 minutes
15. additionSubsequently, 3.2 ml of a DMSO solution of 2-M anhydrous H3PO4 was added
16. stirringthe mixture was stirred for further 2 hours
17. extractionThe reaction mixture was extracted with 150 ml of ethyl acetate
18. dry with materialthe extract was dried over anhydrous Na2SO4
19. distillationThe ethyl acetate was distilled off
20. dissolutionthe residue was dissolved in 100 ml of ethanol
21. additionTo this solution was added 50 g of NaHOS3 in 90 ml of water
22. stirringthe mixture was stirred vigorously for 10 minutes
23. additionwas added until the pH value of the liquid
24. waitAfter 5 minutes
25. customthe reaction liquid
26. extractionwas extracted twice with 60 ml of ether
27. distillationthe ether was then distilled off
28. customto leave an oily substance

ORD record

ord-d17c399d4d624da88d4df701a69906bc

Source dataset

uspto-grants-1987_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04687778