Trifluoroacetic acid → HCID 19605035, compound

HRID 1603498Notes

Reaction equation

HRID 1603498 reaction equation
FC(F)(F)C(O)=O.[CH2:8]([O:10][C:11]([C:13]1[N:14]=[C:15]([CH2:23][NH:24][C:25](OC(C)(C)C)=O)[S:16][C:17]=1[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[O:12])[CH3:9]>>[CH2:21]([O:20][C:18]([C:17]1[S:16][C:15]2=[CH:23][N:24]=[CH:25][N:14]2[C:13]=1[C:11]([O:10][CH2:8][CH3:9])=[O:12])=[O:19])[CH3:22]

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 19605047HCID 19605047, compound

Product 1

HCID 19605035HCID 19605035, compoundYield 86.1%

Procedure

A 30 ml potion of trifluoroacetic acid was added to 10.24 g 4,5-bis(ethoxycarbonyl)-2-t-butoxycarbonylaminomethylthiazole, and the mixture was then stirred at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure, and an aqueous saturated sodium hydrogencarbonate solution was then added so as to adjust the pH of the solution to about 8. Further, 150 ml of dichloromethane was added thereto, and a mixture of 27 ml of formic acid and 13.5 ml of acetic anhydride which had been beforehand reacted with each other at 50° C. for 30 minutes was then added at room temperature with vigorous stirring, followed by stirring for additional 1 hour. The organic layer was separated, and the aqueous layer was further extracted with dichloromethane three times. The combined organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. To the resulting unpurified 4,5-bis(ethoxycarbonyl)-2-(formylamino)methylthiazole, 30 ml of toluene and 13.3 ml of phosphorus oxychloride were added, followed by stirring at 100° C. for 80 minutes. After cooled to room temperature, the reaction solution was concentrated under reduced pressure, and the resulting residue was then diluted with dichloromethane. Afterward, an aqueous potassium carbonate solution was added so as to adjust the pH of the solution to about 8. The organic layer was separated, and it was further extracted four times from the aqueous layer with dichloromethane. The combined organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The resulting residue was purified by a silica gel column chromatograph to obtain 6.6 g of the title compound.

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure
  2. additionan aqueous saturated sodium hydrogencarbonate solution was then added so as
  3. additionFurther, 150 ml of dichloromethane was added
  4. additiona mixture of 27 ml of formic acid and 13.5 ml of acetic anhydride which
  5. customhad been beforehand reacted with each other at 50° C. for 30 minutes
  6. additionwas then added at room temperature with vigorous stirring
  7. stirringby stirring for additional 1 hour
  8. customThe organic layer was separated
  9. extractionthe aqueous layer was further extracted with dichloromethane three times
  10. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. customthe solvent was evaporated under reduced pressure
  13. additionTo the resulting unpurified 4,5-bis(ethoxycarbonyl)-2-(formylamino)methylthiazole, 30 ml of toluene and 13.3 ml of phosphorus oxychloride were added
  14. stirringby stirring at 100° C. for 80 minutes
  15. temperatureAfter cooled to room temperature
  16. concentrationthe reaction solution was concentrated under reduced pressure
  17. additionthe resulting residue was then diluted with dichloromethane
  18. additionAfterward, an aqueous potassium carbonate solution was added so as
  19. customThe organic layer was separated
  20. extractionit was further extracted four times from the aqueous layer with dichloromethane
  21. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  22. filtrationfiltered
  23. customthe solvent was evaporated under reduced pressure
  24. customThe resulting residue was purified by a silica gel column chromatograph

Sources & evidence

ORD record
ord-7fd1e8ed8e6841ec85e31ce754eb94f0
Source dataset
uspto-grants-1999_11
Patent number
US05990101

Reaction notes

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