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

Temperature

0 °C

A mixture of 3-fluoro-5-trifluoromethyl-phenylamine (9.7 g, 54 mmol) in trifluoroacetic acid (100 mL) was cooled at 0° C. To the mixture was slowly added concentrated hydrochloric acid (10 mL), followed by a solution of sodium nitrite (4.7 g, 68 mmol) in water (5 mL) dropwise over 20 minutes. The mixture was stirred for another 10 minutes at 0° C., 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, 93 mmol) and copper(I) chloride (100 mg, 0.74 mmol) at 0° C. The resulting reaction mixture was allowed to warm to room temperature and stirred for 15 hours. Water (200 mL) was added, and the resulting mixture 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-fluoro-5-trifluoromethyl-benzenesulfonyl chloride (3.7 g, 26%) as a white solid (reference: Cherney, R. J. et al., J. Med. Chem. 46 (2003) 1811). 1H NMR (400 MHz, CDCl3) δ ppm 8.15 (s, 1H); 7.97-7.99 (d, J=4.0 Hz, 1H); 7.74-7.76 (d, J=4.0 Hz, 1H).

1. customThe resulting reaction mixture
2. temperatureto warm to room temperature
3. stirringstirred for 15 hours
4. extractionthe resulting mixture 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-2c82a328213b44d6b618867a2907304c

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08263656B2