1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-[4-(4-Ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzoyl]piperazin-2-one

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Reaction Steps

N,N-Diisopropylethylamine (2.8 mL, 16 mmol), piperazin-2-one (780 mg, 7.8 mmol), EDCI (1.5 g, 7.8 mmol) and HOBt (1.05 g, 7.8 mmol) were successively added to a solution of 4-(4-ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzoic acid (which may be prepared in accordance with the experimental described in Example 4, step 4; 2.0 g, 6.5 mmol) in dichloromethane (22 mL). The reaction mixture was stirred at room temperature overnight and then diluted by addition of dichloromethane (50 mL) and a saturated solution of sodium hydrogen carbonate (50 mL). After separation, the aqueous layer was extracted with dichloromethane (2×50 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated under vacuum. The residue was purified by chromatography on silica gel, using dichloromethane/petroleum ether (80/20) to dichloromethane (100%) to dichloromethane/methanol (98:2 to 95:5) as eluent. The title product was obtained as a yellow solid (2.0 g, 80%).

Provenance & Evidence