Sulfur Dioxide → 2,6-Difluorobenzenesulfonyl chloride

Temperature

-78 °C

To a cooled solution of 1,3-difluorobenzene (9.4 g, 82 mmol) in diethyl ether (120 mL) was added n-BuLi in hexane (32.3 mL, 81 mmol) dropwise at −78° C. The reaction mixture was stirred at −78° C. for 3 h. Sulfur dioxide (106 g, 1648 mmol) was flushed into the solution and stirred at −60° C. for 20 mins, which produced a white solid. NCS (12.10 g, 91 mmol) was added and the reaction mixture was warmed to rt and for 1 h. The reaction mixture with white solid changed to pale brown solution. The reaction mixture was filtered and concentrated to give crude 2,6-difluorobenzenesulfonyl chloride, which was added dropwise into methyl 3-amino-2-fluorobenzoate (5.19 g, 30.7 mmol) in pyridine (50 mL) at 15° C. After the addition, the reaction mixture was stirred at room temperature overnight. Ethyl acetate (100 mL) was added to the reaction mixture and then followed by 40 mL of cold water. The mixture was heated to 55° C. with stirring until all red solids dissolved. The upper layer was organic layer which was isolated and washed again with water. The organic layer was dried and evaporated under reduced pressure. Petro ether was added to the crude product and heated to reflux and then cooled to 5° C. The solids were filtered and rinsed with petro ether to afford methyl 3-(2,6-difluorophenylsulfonamido)-2-fluorobenzoate (6.91 g, 10.35 mmol, 12.56% yield) as orange solid. LCMS: [M+NH4]+=363.0.

1. stirringstirred at −60° C. for 20 mins
2. customwhich produced a white solid
3. temperaturethe reaction mixture was warmed to rt and for 1 h
4. filtrationThe reaction mixture was filtered
5. concentrationconcentrated

ORD record

ord-19d482311646441891b2cabd0fa0af39

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08389723B1