2-Aminothiazole → (E)-3-cyclooctyl-2-(4-methanesulfonyl-phenyl)-N-thiazol-2-yl-acrylamide

Participants

Reaction Conditions

Reaction Steps

A solution of triphenylphosphine (2.09 g, 8 mmol) in methylene chloride (25 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (1.42 g, 8 mmol). The reaction mixture was stirred at 0° C. for 30 min and then treated with a solution of (E)-3-cyclooctyl-2-(4-(methanesulfonyl)-phenyl)-acrylic acid (1.345 g, 4 mmol) in methylene chloride (10 mL). The clear solution was stirred for 15 min at 0° C. and then allowed to warm to 25° C. where it was stirred for 1.5 h. The reaction mixture was then treated with 2-aminothiazole (1.2 g, 12 mmol), and the resulting suspension was stirred for 2 d at 25° C. The reaction mixture was then concentrated in vacuo to remove methylene chloride, and the residue was diluted with ethyl acetate (100 mL) and a 1N aqueous hydrochloric acid solution (100 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×50 mL). The combined organic extracts were successively washed with a saturated aqueous sodium bicarbonate solution (1×150 mL) and a saturated aqueous sodium chloride solution (1×100 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 5/1 to 3/2 hexanes/ethyl acetate) afforded (E)-3-cyclooctyl-2-(4-methanesulfonyl-phenyl)-N-thiazol-2-yl-acrylamide (1.22 g, 73%) as an amorphous solid: EI-HRMS m/e calcd for C21H26N2O3S2 (M+) 418.1385, found 418.1385.

Provenance & Evidence