Trifluoroacetic acid → (2R)-2-(3-chloro-4-methylsulfonylphenyl)-3-cyclopentyl-N-[5-[(Z)-N-hydroxy-C-methylcarbonimidoyl]pyrazin-2-yl]propanamide

Participants

Reaction Conditions

Reaction Steps

A solution of N-[5-(1-tert-butoxyimino-ethyl)-pyrazin-2-yl]-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (195.5 mg, 0.38 mmol) in methylene chloride (1.4 mL) was treated with trifluoroacetic acid (2.8 mL). The resulting reaction mixture was stirred at 25° C. for 2 h, at which time, thin layer chromatography still indicated the presence of starting material. The reaction was then heated at 40° C. where it was stirred overnight. At this time, thin layer chromatography again still indicated the presence of starting material. The reaction mixture was then heated at 60° C. where it was stirred for a second night. The reaction mixture was then allowed cool to 25° C. The reaction mixture was diluted with ethyl acetate (50 mL), and the organic layer was washed with a saturated aqueous sodium bicarbonate solution (2×50 mL) and a saturated aqueous sodium chloride solution (1×50 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40L, Silica, 1/2 ethyl acetate/hexanes) afforded the 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(1(Z)-hydroxyimino-ethyl)-pyrazin-2-yl]-propionamide (110.0 mg, 63%) as an off-white powdery solid: mp 94.2–102.5° C. (foam to gel); (ES)+-HRMS m/e calcd for C21H25ClN4O4S (M+H)+ 465.1358, found 465.1363.

Provenance & Evidence