Imidazole → 3-Benzofuran-2-yl-1-(4-methoxy-benzene sulfonyl)-2,3,4,7-tetrahydro-1H-azepine-2-carboxylic acid tert-butyl ester

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Reaction Steps

To a stirred solution of 1-(4-Methoxy-benzenesulfonyl)-2,3,4,7-tetrahydro-1H-azepine-2,3-dicarboxylic acid 2-tert-butyl ester (0.7 g, 1.59 mmoL) in 1.7 mL of dimethylformamide at 0° C. was added Imidazole (238 mg, 3.5 mmoL) and tert-Butyldimethlysilyl chloride (263 mg, 1.74 mmoL). The reaction was warmed to ambient temperature after one hour, and diluted with ethyl acetate after four hours. The reaction was washed sequentially with water, ammonium chloride, and brine. The organic layer was dried over anhydrous magnesium chloride, filtered and the solvent evaporated under reduced pressure. The crude was stored under high vacuum for 18 hours. The residue was then dissolved in dichlormethane and cooled to 0° C. To this solution was added catalytic dimethylformamide and (0.708 mL, 1.41 mmoL) of 2.0M oxalyl chloride. The reaction was warmed to ambient temperature after 30 minutes, and the solvent was evaporated under reduced pressure after three hours. The acid chloride was azeotroped twice with toluene and dissolved in one mL of toluene. This solution was added to a refluxing suspention of Benzene triphenylphosphine phenol (633 mg, 1.41 mmoL) and Triethylamine (0.59 mL, 4.23 mmoL) in 5.65 mL toluene. The reaction was kept at reflux for 2.5 hours and slowly cooled to ambient temperature over 18 hours. The reaction was then diluted with ethyl acetate and washed sequentially with 1N HCL, half saturated sodium bicarbonate, 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: 5% to 15% ethyl acetate in hexanes) to yield 3-Benzofuran-2-yl-1-(4-methoxy-benzene sulfonyl)-2,3,4,7-tetrahydro-1H-azepine-2-carboxylic acid tert-butyl ester; MS: (M+H)+ =484, (M+NH4)+ =501.

Provenance & Evidence