3-Thiophenesulfonyl chloride, 2-chloro- synthesis

Yield:-

Reaction Conditions:

Stage #1:3-bromo-2-chlorothiophene with n-butyllithium in tetrahydrofuran at -78; for 0.75 h;
Stage #2: with sulfur dioxide in tetrahydrofuran at -78; for 1 h;
Stage #3: with N-chloro-succinimide in tetrahydrofuran at 0; for 2 h;

Steps:

1 Step-1:
To a stirred solution of 3-bromo-2-chlorothiophene (1 g, 5mmol) in THF (10 ml_) was added n-BuLi (4.1 mL, 6.5 mmol, 1.6 M) at -78 °C and stirred for 45 min at the same temperature. The SO2 gas was passed through the reaction mixture for 1 h, at the same temperature. NCS (0.67 g, 5mmol) was the added to the reaction mixture and allowed to stir at 0 °C for 2 h. After completion of the reaction as indicated by TLC, the reaction mixture was poured into water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over Na2SO4 and evaporated under vacuum to give crude product (1.31 g, 100 %). It was used immediately for the next step without analysis.

References:

OXFORD DRUG DESIGN LIMITED WO2021/123237, 2021, A1 Location in patent:Page/Page column 212