Trifluoroacetic acid → Ethyl 2-(formylamino)methylthiazole-4-carboxylate

Participants

Reaction Steps

To 1.50 g of the above-obtained ethyl 2-(tert-butoxycarbonylamino)methylthiazole-4-carboxylate was added 5 ml of trifluoroacetic acid, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was concentrated under reduced pressure. A saturated aqueous solution of sodium hydrogencarbonate was added to the residue to adjust the pH of the mixture to approximately 8. To this was added 30 ml of dichloromethane. To the mixture was added with vigorous stirring a mixture which had been prepared by reacting 1 ml of formic acid with 1 ml of acetic anhydride at 50° C. for 30 minutes, and the resulting mixture were stirred for an additional one hour. The organic layer was separated, and the aqueous layer was extracted twice with dichloromethane. The combined organic layers were dried over anhydrous magnesium sulfate, and concentrated to dryness under reduced pressure to give 1.15 g of crude ethyl 2-(formylamino)methylthiazole-4-carboxylate. This compound was dissolved in 30 ml of dichloromethane. To the solution was added 1.2 ml of phosphorus oxychloride at -20 C., and the mixture was stirred at room temperature for 30 minutes. The reaction solution was concentrated under reduced pressure. To this was added 12 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 30 ml of water, and the solution was washed with 20 ml of dichloromethane. To this was added sodium hydrogencarbonate to adjust the pH of the solution to 8, and the mixture was extracted with dichloromethane (30 ml×2). The combined organic layers were dried over anhydrous magnesium sulfate, and concentrated to dryness under reduced pressure to give 0.885 g (yield 85%) of the title compound as light brown crystals.

Provenance & Evidence