Cyclopropanesulfonyl chloride synthesis

Yield:-

Reaction Conditions:

Stage #1:cyclopropylmagnesium bromide with sulfur dioxide in tetrahydrofuran at -10 - 20; for 0.666667 h;
Stage #2: with N-chloro-succinimide in tetrahydrofuran at -5 - 20;

Steps:

11a.2A
To a solution of cyclopropylmagnesium bromide (0 5 M 20 mL, 10 0 mmol) in anhydrous THF (10 mL) at about -10⁰C is added a solution of SO; in THF (~ 16 wt%, 4 8 mL, 12 mmo.) slowiy over 10 mm at -10 to -5°C Tne reaction mixture is warmed to ambient temperature over 0 5h, and then NCS (2 O g 15 mmo.) is added at about -5 to 0°C The reaction mixture is warmed up to ambient temperature and diluted with 50 mL oi methyl terl-buty. ether To tne reaction mixture ι≤ added 50 mL water and the mixture is stirred for 5 mm The organic layer is washed with 50 mL of bnne The organic layer is concentrated and the resultant cyclopropylsuifony. chloride is dissolved in CH₂Ci₂ (total volume was about 50 mL) and ammonia gas is bubbled in at about O'C for about 5 mm and the mixture is slowly warmed up to ambient temperature and stored at that temperature for 2 h The mixture is filtered through Cehte to remove the solid (NH₄C.), and the filtrate is concentrated to obtain a crude cyclopropyisulfonamide solid (~ 1 2g) Re-cryslailization of the crude product from EtOAc/hexane produces cyclopropyisuifonarnide 42 in 80% overall yield.

References:

BOEHRINGER INGELHEIM INTERNATIONAL GMBH;O'MEARA, Jeffrey;BORDELEAU, Josée;GORYS, Vida;LEBLANC, Mélissa;LENHARDT, Kirsten;LLINAS-BRUNET, Montse;PARISIEN, Mathieu;POUPART, Marc-André WO2010/34105, 2010, A1 Location in patent:Page/Page column 57-58

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