Citric Acid → Acetic acid 2-hydroxycarbamoyl-1-(4-methoxy-benzenesulfonyl)-2,3,4,7-tetrahydro-1H-azepin-3-ylmethyl ester

Participants

Reaction Steps

To a solution of 3-Acetoxymethyl-1-(4-methoxy-benzenesulfonyl)-2,3,4,7-tetrahydro-1H-azepine-2-carboxylic acid (101 mg, 0.263 mmoL) in 3 mL dimethylformamide at -20° C. under an argon blanket was added O-(tert-Butyldimethyl-silyl)hydroxylamine (50 mg, 0.342 mmoL) followed by N,N-Diisopropylethylamine (0.069 mL, 0.342 mmoL). (O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate) (110 mg, 0.289 mmoL) was added in and the temperature was kept at -20° C. for 40 minutes before allowing to warm to ambient temperature. The reaction was allowed to stir for 19 hours at which time it was diluted with ethyl acetate. 10% citric acid was added in and stirred for 30 minutes, the reaction was then washed sequentially with water, 0.5N HCL, dilute sodium bibarbonate, and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered, and the solvent removed under reduced pressure. The residue was purified by column chromatography (silica: 0.5% to 3% methanol in dichloromethane) to yield (33 mg, 31%) of Acetic acid 2-hydroxycarbamoyl-1-(4-methoxy-benzenesulfonyl)-2,3,4,7-tetrahydro-1H-azepin-3-ylmethyl ester; MS: (M+H)+ =399, (M+NH4)+ =416.

Provenance & Evidence