Trifluoroacetic acid → HCID 19605126, compound

Participants

Reaction Conditions

Reaction Steps

A 25 ml potion of trifluoroacetic acid was added to 1.64 g of 2-(N-t-butoxycarbonylamino)methyl-5-phthalimidomethylthiazole under ice-cooling, and the mixture was then allowed to stand at room temperature for 1 hour. The solvent was evaporated under reduced pressure, and to the resulting residue, 75 ml of dichloromethane and 25 ml of an aqueous saturated sodium bicarbonate solution were added under ice-cooling, followed by stirring. After the aqueous layer was separated, the organic layer was similarly washed once with the aqueous saturated sodium bicarbonate solution, dried over anhydrous sodium sulfate, and then filtered, and the solvent was evaporated under reduced pressure. Afterward, 997 mg of the resulting residue was dissolved in 9 ml of dichloromethane, and a mixed acid anhydride solution comprising a mixed solution of 0.446 ml of acetic anhydride and 0.446 ml of formic acid which had been beforehand reacted with each other at 50° C. for 30 minutes was then added thereto under ice-cooling. After 2 hours, 9 ml of the aqueous saturated sodium bicarbonate solution was added to the reaction solution. The solution was extracted with dichloromethane (9 ml×2). The combined organic layer was washed with the aqueous saturated sodium bicarbonate solution, dried over anhydrous sodium sulfate, and then filtered, and the solvent was evaporated under reduced pressure. Then, to 1.22 g of the resulting residue, 8.9 ml of phosphorus oxychloride was added, followed by stirring under heating at 100° C. for 1 hour. The reaction solution was concentrated under reduced pressure, and the resulting residue was then diluted with 21 ml of dichloromethane under ice-cooling. To this solution, 9 ml of the aqueous saturated sodium bicarbonate solution and 3.2 ml of an aqueous saturated potassium carbonate solution were added under ice-cooling, and after stirring, the organic layer was separated. Furthermore, the aqueous layer was extracted with dichloromethane (27 ml×2). The combined organic layer was washed with the aqueous saturated sodium bicarbonate solution, and the organic layer was dried over anhydrous sodium sulfate, and then filtered. Afterward, the solvent was evaporated under reduced pressure, and the resulting residue was then purified by a silica gel column chromatograph and Cephadex LH-20 in succession to obtain 412 mg of 2-phthalimidomethylimidazo[5,1-b]thiazole.

Provenance & Evidence