Cesium carbonate → 4-chloro-N-(2,3-difluoro-4-(oxazol-2-yl)benzyl)-N-(trans-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide

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Reaction Steps

A suspension of 4-chloro-N-((1R,2R)-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide Compound 15 (130 mg, 0.43 mmol), cesium carbonate (167 mg, 0.51 mmol), and 2-(4-(bromomethyl)-2,3-difluorophenyl)oxazole (141 mg, 0.51 mmol) in dimethylformamide (2 mL) was stirred for 2 h. The reaction was partitioned between ethyl acetate and saturated sodium bicarbonate, dried over magnesium sulfate, concentrated and purified by flash chromatography on silica gel using a gradient of 0 to 100% ethyl acetate in hexane to give 4-chloro-N-(2,3-difluoro-4-(oxazol-2-yl)benzyl)-N-((1R,2R)-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide (100 mg, 47%). Recrystallization from methanol yielded a crystalline product which was analyzed by X-Ray crystallography, verifying the stereochemistry as R,R. 1H NMR (400 MHz, CDCl3) δ ppm 7.77-7.83 (m, 2H), 7.75 (m, 2H), 7.51-7.57 (m, 1H), 7.50 (m, 2H), 7.32 (s, 1H), 4.60 (d, J=15.86 Hz, 1H), 4.40 (d, J=15.86 Hz, 1H), 3.57-3.66 (m, 2H), 2.98-3.17 (m, 1H), 2.45-2.63 (m, 1H), 1.59-1.75 (m, 3H), 1.39-1.54 (m, 2H), 0.98-1.21 (m, 4H). MS [M+H]+=497. HRMS [M+H]+ calc'd 497.1113, found 497.1093. Chiral LC: R.T.=8.21 min, 100% ee.

Provenance & Evidence