Oxalyl chloride → 4-(3-{4-[(tert-Butoxycarbonyl-cyclopropyl-amino)-methyl]-piperidin-1-yl}-3-oxo-propyl)-3-methyl-benzoic Acid Methyl Ester

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Reaction Steps

Oxalyl chloride (1.26 ml, 14.4 mmol) was added to a solution of 4-(2-carboxy-ethyl)-3-methyl-benzoic acid methyl ester from Example E30.3 (1.60 g, 7.2 mmol) in dichloromethane (50 ml) and few drops of DMF. The mixture was stirred for 1 h at room temperature, concentrated in vacuo and azeotroped with toluene. The residue was dissolved in dichloromethane (50 ml) and DIEA (2.5 ml, 14.4 mmol) and cyclopropyl-piperidin-4-ylmethyl-carbamic acid tert-butyl ester from Example E38 (1.83 g, 7.2 mmol) in dichloromethane (5 ml) was added. The mixture was stirred for 2 h at room temperature, diluted with dichloromethane, washed with saturated NaHCO3 then brine, dried and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; 50% EtOAc:50% cyclohexane) to yield the title compound (1.42 g, 43%).

Provenance & Evidence