Diisopropylethylamine → Ethyl 8-bromo-6-chloro-7-(4-(6-(4-chlorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylate

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Reaction Steps

A solution of 4-(8-bromo-6-chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (0.18 g, 0.40 mmol) in thionyl chloride (5 mL) was stirred and heated to gentle reflux for 30 minutes. The solution was cooled to ambient temperature and concentrated. The residual light yellow solid was dissolved in dichloromethane (4 mL). To the resulting stirred solution at ambient temperature was added 6-(4-chlorophenyl)pyridin-2-amine hydrochloride (96.6 mg, 0.40 mmol), followed by N,N-diisopropylethylamine (0.28 mL, 1.60 mmol). A solution formed, and stirring was continued at ambient temperature for 3 hours. The solution was diluted with ethyl acetate (20 mL) and 1M hydrochloric acid (10 mL), then transferred to a separatory funnel. After shaking, the organic layer was washed successively with 10 mL portions of water, 10% sodium carbonate, and brine, dried over sodium sulfate and evaporated. The residual oil was purified by chromatography on silica gel, eluting with 80/20 hexanes/ethyl acetate, to afford the desired compound as a colorless oil (0.15 g, 58% yield).

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