5-Methylhexanoic acid → 5-Methylhexanoyl chloride

Participants

Reaction Steps

To a solution of 5-methylhexanoic acid (0.53 g, 4 mmole) in dichloromethane was added oxalyl chloride (0.77 g, 6 mmole). The reaction mixture was stirred at room temperature for 2 hours and then evaporated under vacuum to give crude 5-methylhexanoyl chloride. To a solution of 4,4-bis(trifluoromethyl)-2-(4-fluorophenyl)-4,5-dihydro-5-amine-N,N-1,5-dimethyl-1H-imidazole (0.60 g, 1.76 mmole) in dichloromethane (15 mL) was added 5-methylhexanoyl chloride and pyridine (0.42 g, 5 mmole). The reaction mixture was stirred overnight at room temperature under nitrogen. The crude reaction mixture was quenched with water and extracted with ether. The organic layer was washed successively with water, sodium hydroxide (1N) and saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated under vacuum. The residue was purified by flash chromatography eluting with hexane and hexane-ethyl acetate (20:1 to 50:50). The crude product (0.42 g, 85%) was treated with HCl in ether and recrystallized from dichloromethane-methanol-petroleum ether to give the title compound as a white solid: mp 112°-114°; MS m/e 456 (M+ +H); 1H NMR (CDCl3 /TMS) δ 0.90(s,3H,CH3), 0.93(s,3H,CH3), 1.27(m,2H,CH2), 1.67(m,3H,CH2CH), 2.47(m,2H,CH2), 3.00(s,3H,NCH3), 3.23(s,3H,NCH3), 7.03(s,1H,CH), 7.33(m,2H,Harom), 8.00(m,2H,Harom).

Provenance & Evidence