Triethylamine → methyl (R)-3-methoxy-4-[1-methyl-5-(2-methyl-4,4,4-trifluorobutylcarbamoyl)indol-3-ylmethyl]benzoate

Participants

Reaction Steps

A mixture of (R)-2-methyl-4,4,4-trifluorobutylamine hydrochloride (9.79 g), methyl 4-(5-carboxy-1-methylindol-3-ylmethyl)-3-methoxybenzoate (20.55 g), 4-dimethylaminopyridine (7.45 g), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (15.07 g) and triethylamine (9.3 mL) was dissolved in dry methylene chloride (240 mL) and the solution was stirred under an inert atmosphere for 18 h. The mixture was diluted with methylene chloride (200 mL) and washed twice with 1N hydrochloric acid. The combined acid washes were back extracted with methylene chloride and the combined organic extracts were washed (water, brine), dried (MgSO4), and evaporated. The residue was purified by flash chromatography, eluting with 97:3 methylene chloride:ethyl acetate to give methyl (R)-3-methoxy-4-[1-methyl-5-(2-methyl-4,4,4-trifluorobutylcarbamoyl)indol-3-ylmethyl]benzoate (14.48 g, 55%) as a white solid; mp 150°-151° C.; partial NMR (300 MHz, CDCl3): 1.12 (d, 3H, CH3), 1.98-2.08 (m, 1H, CHCH3) 2.12-2.44 (m, 2H, CF3CH2), 3.30-3.58 (m, 2H, CH2N), 3.76 (s, 3H, NCH3), 3.90 (s, 3H, OCH3), 3.93 (s, 3H, OCH3), 4.13 (s, 2H, ArCH2Ar'), 6.23 (br t, 1H, NHCO).

Provenance & Evidence