Trifluoroacetic acid → HCID 19605056, compound

A 30 ml portion of trifluoroacetic acid was added to 9.0 g of 2-(N-t-butoxycarbonylamino)methyl-4-ethoxycarbonyl-5-methylthiazole, and the mixture was then stirred at room temperature for 1 hour. After the reaction solution was concentrated under reduced pressure, an aqueous saturated sodium hydrogencarbonate solution was added so as to adjust the pH of the solution to about 8. Then, 150 ml of dichloromethane was added, and a mixture of 28.4 ml of formic acid and 14.2 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 four times with dichloromethane. 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-ethoxycarbonyl-2-(formylamino)methyl-5-methylthiazole, 30 ml of toluene and 14 ml of phosphorus oxychloride were added, followed by stirring at 100° C. for 1 hour. 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 the aqueous layer was further extracted five times with dichloromethane. The combined organic layer was dried over anhydrous magnesium sulfate and then filtered, and the solvent was evaporated under reduced pressure to obtain 5.43 g of 3-ethoxycarbonyl-2-methylimidazo[5,1-b]thiazole.

1. concentrationAfter the reaction solution was concentrated under reduced pressure
2. additionan aqueous saturated sodium hydrogencarbonate solution was added so as
3. additionThen, 150 ml of dichloromethane was added
4. additiona mixture of 28.4 ml of formic acid and 14.2 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 four times with dichloromethane
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-ethoxycarbonyl-2-(formylamino)methyl-5-methylthiazole, 30 ml of toluene and 14 ml of phosphorus oxychloride were added
14. stirringby stirring at 100° C. for 1 hour
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. extractionthe aqueous layer was further extracted five times with dichloromethane
21. dry with materialThe combined organic layer was dried over anhydrous magnesium sulfate
22. filtrationfiltered
23. customthe solvent was evaporated under reduced pressure

ORD record

ord-09cdb6b462e3418cb1cb01a1a53d2cee

Source dataset

uspto-grants-1999_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05990101