5-chloro-N-cyclopropylsulfonyl-2,4-difluorobenzamide

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the procedure as described in Example 8 and making variations as required to replace 5-chloro-2,4-difluoro-N-(methylsulfonyl)benzamide with 5-chloro-N-(cyclopropylsulfonyl)-2,4-difluorobenzamide and to replace adamantan-1-ylmethanol with spiro[2.5]octan-6-ylmethanol, the title compound was obtained as a colorless solid (0.165 g, 28%): 1H NMR (300 MHz, CDCl3) δ8.72-8.59 (m, 1H), 8.16-8.07 (m, 1H), 6.76-6.65 (m, 1H), 3.97-3.86 (m, 2H), 3.17-3.05 (m, 1H), 2.03-1.72 (m, 5H), 1.51-1.42 (m, 2H), 1.36-1.11 (m, 4H), 1.00-0.90 (m, 2H), 0.38-0.14 (m, 4H); MS (ES+) m/z 416.2, 418.2 (M+1).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5-chloro-2,4-difluorobenzoic acid (10.0 g, 51.93 mmol) and 1,1′-carbonyldiimidazole (10.11 g, 62.32 mmol) was stirred at reflux for 2 hours, cooled to ambient temperature, and cyclopropanesulfonamide (7.55 g, 62.32 mmol) was added. The reaction mixture was stirred at ambient temperature for 16 hours, diluted with ethyl acetate (300 mL), washed with 1M aqueous hydrochloric acid, brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was re-crystallized from ethyl acetate/hexanes mixture (1:2) to afford the title compound as a colorless solid (7.7 g, 56%): MS (ES−) m/z 294.1 (M−1). at reflux for 2 hours The reaction mixture was stirred at ambient temperature for 16 hours washed with 1M aqueous hydrochloric acid, brine dried over anhydrous magnesium sulfate filtered concentrated in vacuo The residue was re-crystallized from ethyl acetate/hexanes mixture (1:2)