MacaMide IMpurity 10 synthesis

Yield:883715-22-8 75%

Reaction Conditions:

Stage #1:linoleic acid with 1,1'-carbonyldiimidazole in dichloromethane at 20; for 2 h;
Stage #2:3-METHOXYBENZYLAMINE with dmap in dichloromethane at 20; for 18 h;

Steps:

4.1.1. N-benzylpalmitamide (3a)
General procedure: To a solution of palmitic acid (300mg, 1.17mmol) in dichloromethane (DCM, 10mL) was added 1,1′-carbonyldiimdazole (209mg, 1.29mmol). The reaction was stirred at room temperature for 2h. The reaction mixture was slowly added to a solution of benzylamine (153μL, 1.40mmol) and 4-dimethylaminopyridine (14mg, 0.12mmol) in dichloromethane (5mL). The solution was stirred at room temperature for 18h. DCM (100mL) and saturated aqueous NaHCO₃ (30mL) were added to the reaction mixture. The organic layer was separated and washed with H₂O (30mL), brine (30mL), dried over anhyd sodium sulfate, filtered, and concentrated to dryness under reduced pressure. The crude was purified by flash chromatography on silica gel eluting with hexane/EtOAc (3:1, v/v) to give the title compound as a white solid (578mg, 86%). Mp 85-87° [lit.⁴⁵ mp 94.5-95°, and⁴⁶ fp 95.1°]; ¹H NMR (400MHz, CDCl₃) δ 7.32-7.36 (m, 2H), 7.26-7.30 (m, 3H), 5.72 (br s, 1H), 4.45 (d, J=6.0Hz, 2H), 2.21 (t, J=7.2Hz, 2H), 1.61-1.67 (m, 2H), 1.25-1.34 (m, 24H), 0.88 (t, J=6.8Hz, 3H); ¹³C NMR (CDCl₃, 100MHz) δ 173.21, 138.66, 128.92, 128.05, 127.71, 43.80, 37.06, 32.16, 29.92, 29.89, 29.84, 29.73, 29.59, 29.56, 26.01, 22.93, 14.36; LCMS, C₂₃H₃₉NO, [M+H]: 346.

References:

Wu, Hui;Kelley, Charles J.;Pino-Figueroa, Alejandro;Vu, Huyen D.;Maher, Timothy J. [Bioorganic and Medicinal Chemistry,2013,vol. 21,# 17,p. 5188 - 5197]

FullText