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0 °C

To a solution of 4-(4-ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzoic acid (55 mg, 0.18 mmol; which may be prepared as described in D2) in dichloromethane (1.8 mL) under Argon cooled at 0° C. were added oxalyl chloride (2M in dichloromethane, 135 μL, 0.27 mmol) and a drop of N,N-dimethylformamide. The mixture was allowed to come to room temperature over 2 hours, and then piperazin-2-one (20 mg, 0.20 mmol) followed by diisopropylethylamine (93 μL, 0.53 mmol) were added. The reaction mixture was cooled to 0° C. and a solution of 1N HCl was added. After stirring a few minutes, dichloromethane was added and the aqueous layer (pH 7) was extracted twice with dichloromethane. The combined organic phases were dried over sodium sulfate, filtrated and concentrated in vacuo. The residue was purified by preparative thin layer chromatography on silica gel, using dichloromethane/methanol (95:5) as eluent. The title product was obtained as a yellow oil (38 mg, 55%).

1. additionwere added
2. extractionthe aqueous layer (pH 7) was extracted twice with dichloromethane
3. dry with materialThe combined organic phases were dried over sodium sulfate
4. filtrationfiltrated
5. concentrationconcentrated in vacuo
6. customThe residue was purified by preparative thin layer chromatography on silica gel