Trifluoroacetic acid → HCID 22916697, compound

To 0.66 g of the above-obtained 2-(tert-butoxycarbonylamino)methyl-4-fluoromethylthiazole was added 2 ml of trifluoroacetic acid, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was concentrated under reduced pressure. To the residue was added a saturated aqueous solution of sodium hydrogencarbonate to adjust the pH of the mixture to approximately 8. To this reaction solution was added 20 ml of dichloromethane. To the mixture was added with stirring a solution which had been prepared in advance by reacting 0.33 ml of formic acid with 0.33 ml of acetic anhydride at 50° C. for 10 minutes, and the resulting mixture was stirred at room temperature for an additional one hour. The organic layer was separated, and the aqueous layer was extracted with dichloromethane (10ml×2). The combined organic layers were dried over anhydrous magnesium sulfate, and concentrated to dryness under reduced pressure to give 0.27 g of crude 3-fluoromethyl-2-(formylamino)methylthiazole. This compound was dissolved in 6 ml of dichloromethane. 4.2 ml of phosphorus oxychloride was added to the solution at -20° C., and the mixture was stirred at room temperature for 30 minutes. The reaction solution was concentrated under reduced pressure. To the residue was added 4.2 ml of phosphorus oxychloride, and the mixture was stirred at 100° C. for 30 minutes. The reaction solution was cooled to room temperature, and then concentrated to dryness under reduced pressure. The residue was dissolved in 10 ml of water, and the solution was washed with 5 ml of dichloromethane. To this was added a saturated aqueous solution of sodium hydrogencarbonate to adjust the pH to approximately 8. The mixture was further extracted with dichloromethane (10ml×2). The combined organic layers were dried over anhydrous magnesium sulfate, and concentrated to dryness under reduced pressure to give 0.241 g (yield 58%) of the title compound.

1. concentrationThe reaction solution was concentrated under reduced pressure
2. additionTo the residue was added a saturated aqueous solution of sodium hydrogencarbonate
3. additionTo this reaction solution was added 20 ml of dichloromethane
4. additionTo the mixture was added
5. stirringwith stirring a solution which
6. customhad been prepared in advance
7. customat 50° C.
8. customfor 10 minutes
9. stirringthe resulting mixture was stirred at room temperature for an additional one hour
10. customThe organic layer was separated
11. extractionthe aqueous layer was extracted with dichloromethane (10ml×2)
12. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
13. concentrationconcentrated to dryness under reduced pressure

ORD record

ord-318ae9e9784a46d6957ee76defa329ed

Source dataset

uspto-grants-1997_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05663162