Hydrochloric Acid → 3-Methoxy-5-(trifluoromethyl)benzene-1-sulfonyl chloride

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Reaction Conditions

Reaction Steps

3-Methoxy-5-trifluoromethyl-phenylamine (10 g, 54 mmol) was mixed with trifluoroacetic acid (100 mL) in a 250 mL flask. After being cooled to 0° C., to the mixture was slowly added concentrated hydrochloric acid (10 mL), and then added a solution of sodium nitrite (4.7 g, 68 mmol) in water (5 mL) dropwise over 20 min at 0° C. The mixture was stirred for another 10 minutes after the addition and then poured into a stirred mixture of acetic acid (120 mL), sulfurous acid (0.94 N aqueous sulfur dioxide solution, 120 mL), copper(II) chloride (9.2 g) and copper(I) chloride (100 mg) at 0° C. The reaction mixture was allowed to warm to room temperature and stirred for 15 hours, and then water (200 mL) was added. The aqueous layer was extracted with ethyl acetate (100 mL×3). The combined organic layers were dried over sodium sulfate, filtered through a glass funnel and concentrated in vacuo. The residue was purified by column chromatography (20% ethyl acetate in petroleum ether) to afford 3-methoxy-5-trifluoromethyl-benzenesulfonyl chloride (3.9 g, 26.4%) as a white solid (reference: Cherney, R. J. et al., J. Med. Chem. 46 (2003) 1811). 1H NMR (400 MHz, CDCl3) δ ppm 7.89 (s, 1H); 7.70 (s, 1H); 7.50 (s, 1H); 4.00 (s, 3H).

Provenance & Evidence