4-Methylmorpholine → 3-(2-benzyloxy-4-carbamoyl-benzenesulfonylamino)-N-methoxy-N-methyl-succinamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-benzyloxy-4-[(S)-2-tert-butoxycarbonyl-1-(methoxy-methyl-carbamoyl)-ethylsulfamoyl]-benzoic acid (8.0 g, 15.3 mmol) in tetrahydrofuran (150 ml) at 0° C. was added 4-methyl morpholine (2.5 ml, 22.9 mmol), 1-hydroxybenzotriazole (3.09 g, 22.90 mmol), followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (4.40 g, 22.90 mmol). The reaction was stirred for 1 h at 0° C., then concentrated ammonium hydroxide was added (3.1 ml, 22.9 mmol). The reaction was allowed to warm slowly to room temperature and stirred overnight. The reaction was then diluted with ethyl acetate and washed sequentially with 5% citric acid, saturated sodium bicarbonate, and saturated sodium chloride, dried over magnesium sulfate, filtered and concentrated under reduced pressure to yield a pale oil. The crude residue was chromatographed (silica gel with a gradient of 50% ethyl acetate/49% hexane/1% acetic acid to 99% ethyl acetate/1% acetic acid) to give 3-(2-benzyloxy-4-carbamoyl-benzenesulfonylamino)-N-methoxy-N-methyl-succinamic acid tert-butyl ester as a white foam (6.57 g, 82%). 1H NMR(300 MHz, DMSO) 8.12 (s, 1H), 7.76 (d, 1H), 7.38 (m, 9H), 5.34 (dd, 2H), 4.60 (m, 1H), 3.50 (bs, 3H), 2.58 (bs, 3H), 2.55 (dd, 1H), 2.34 (dd, 1H), 1.30 (s, 9H). MS(APCI) m/z 522.2 (M+1), 520.2 (M−H).

Provenance & Evidence