1-Methylimidazole → N-Methyl-5-(1-methyl-1H-imidazol-2-yl)-N-propyl-isophthalamic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

Add n-butyl lithium (2.0 M in pentane, 0.78 mL, 1.55 mmol) dropwise over 30 min to a previously nitrogen-flushed, flame-dried vessel containing 1-methyl-1H-imidazole (0.12 mL, 1.5 mmol) in THF (10 mL) at −78° C., and stir for 30 min at the same temperature. Warm the solution to 0° C. and add dropwise zinc (II) chloride (1.0 M in diethyl ether, 4.5 mL, 4.5 mmol) over 10 min. Stir the mixture at the same temperature for 1 h and at room temperature for 30 min. Add 5-iodo-N-methyl-N-propyl-isophthalamic acid methyl ester (361 mg, 1.0 mmol) and tetrakis(triphenylphosphine)palladium (0) (12 mg) under nitrogen before heating the reaction to reflux for 20 min. Cool to room temperature, concentrate and purify (silica gel chromatography, eluting with 0:100 to 8:92 methanol:dichloromethane) to give the title compound.

Provenance & Evidence