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

Temperature

0 °C

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).

1. additionafter the addition
2. temperatureto warm to room temperature
3. stirringstirred for 15 hours
4. extractionThe aqueous layer was extracted with ethyl acetate (100 mL×3)
5. dry with materialThe combined organic layers were dried over sodium sulfate
6. filtrationfiltered through a glass funnel
7. concentrationconcentrated in vacuo
8. customThe residue was purified by column chromatography (20% ethyl acetate in petroleum ether)

ORD record

ord-f07d77716f0d411db60db2bbf7451bd1

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08268870B2