4-Toluenesulfonyl chloride → {6-Fluoro-4-[1-(toluene-4-sulfonyl)-piperidin-4-yl]-naphthalen-2-yl}-acetic acid methyl ester

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Reaction Steps

Diisopropylethylamine (0.6 mL, 3.4 mmol) was added at 0° C. to a solution of (6-fluoro-4-piperidin-4-yl-naphthalen-2-yl)-acetic acid methyl ester trifluoroacetate salt (which may be prepared as described above; 150 mg, 0.36 mmol) in tetrahydrofuran (5 mL), and the mixture was stirred at room temperature for 30 min. p-Toluenesulfonyl chloride (available from Sigma-Aldrich; 103 mg, 0.54 mmol) was added and the mixture was stirred at room temperature for 16 h. The solvent was evaporated under reduced pressure. Ethyl acetate was added and the mixture was washed with aqueous NaHCO3 (5 mL) and water (5 mL). The organic layer was dried over Na2SO4, filtered, and evaporated under reduced pressure. The residue was purified by chromatography on silica gel using a Biotage purification system, eluting with 12% ethyl acetate/hexanes, to give {6-fluoro-4-[1-(toluene-4-sulfonyl)-piperidin-4-yl]-naphthalen-2-yl}-acetic acid methyl ester (76 mg, 46%) as a white solid. MS cald. for C24H25FNO4S [(M+H)+]: 456, obsd. 456.4.

Provenance & Evidence