2-Bromo-5-chloro-4-fluorobenzenesulfonyl chloride synthesis

Yield:-

Reaction Conditions:

Stage #1: 2-chloro-5-bromofluorobenzenewith sulfuric acid at 110;
Stage #2: with phosphorus pentachloride in 1,2-dichloro-ethane at 110;Inert atmosphere;

Steps:

12 Preparation of 2-bromo-5-chloro-4-fluorobenzene-1-sulfonyl chloride (12-2)

[0265] A mixture of 12-1 (10 g, 48.54 mmol) in fuming sulfuric acid (50 mL) was stirred and heated at 110°C overnight. The mixture was cooled to room temperature and carefully pouredinto ice. The resulting solution was stirred at room temperature for 30 mins, followed by addition of EtOAc. The aqueous layer was isolated and concentrated under vacuum. The precipitate was filtered off and the filtrate was diluted with DCE (100 mL). To the solution PCI5 (16 g, 83.33 mmol) was added which was stirred at 110°C under nitrogen overnight. The mixture was cooled to room temperature and carefully poured into ice. The resulting solutionwas stirred at room temperature for 30 mins, followed by addition of EtOAc. The organic layer was isolated and concentrated in vacuum. The residue was purified by column chromatography on silica gel (PE: EA= 10:1) to give 12-2. ‘H NMR (400 MHz, CDCI3) 5 8.26 (d, J = 7.2 Hz, 1H), 7.65 (d, J = 8.0 Hz, 1H).

References:

WO2015/77905,2015,A1 Location in patent:Paragraph 0265