Potassium tert-butoxide → 7-Bromo-8-chloro-5-oxo-2,3,4,5-tetrahydro-benzo[b]azepine-1,4-dicarboxylic acid 1-isopropyl ester 4-methyl ester

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Reaction Steps

To a heated mixture of potassium t-butoxide (1.27 g, 11.3 mmol) in toluene (50 ml) at 70° C. was added a solution of 5-Bromo-4-chloro-2-[isopropoxycarbonyl-(3-methoxycarbonyl-propyl)-amino]-benzoic acid methyl ester (2.55 g, 5.66 mmol) in toluene (50.0 ml) over 30 minutes. After the addition was completed, the mixture was cooled to room temperature and diluted with ethyl acetate (100 ml), and then washed with 1.00N HCl(aq) (120 ml) and brine (3×120 ml). The organic layer was dried over Na2SO4 and concentrated under reduced pressure. Purification by silica gel chromatography (gradient eluent, 0-15% ethyl acetate in hexane) provided 7-Bromo-8-chloro-5-oxo-2,3,4,5-tetrahydro-benzo[b]azepine-1,4-dicarboxylic acid 1-isopropyl ester 4-methyl ester (1.46 g, 62%) as oil. MS (ES+): 418, 420 (M+H).

Provenance & Evidence