Diisopropylethylamine → {(R)-2-[(E)-3-(5-cyano-2-methoxy-phenyl)-acryloylamino]-3-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-propyl}-carbamic acid tert-butyl ester

Participants

Reaction Steps

A solution of (E)-3-(5-cyano-2-methoxy-phenyl)-acrylic acid (0.36 g, 1.77 mmol), 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyl-uronium tetrafluoroborate (1.01 g, 2.65 mmol) and diisopropylethylamine (0.46 ml, 2.65 mmol) in DCM (15 ml) is treated with a solution of {(R)-2-Amino-3-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-propyl}-carbamic acid .tert.-butyl ester (0.65 g, 1.77 mmol) in DCM (5 ml). The reaction mixture is stirred at ambient temperature for 30 minutes, then washed with saturated aqueous NaHCO3, water and brine. The DCM phase is dried over MgSO4 and evaporated. The crude product is purified by flash silica chromatography (elution with 2% methanol in DCM) to afford {(R)-2-[(E)-3-(5-cyano-2-methoxy-phenyl)-acryloylamino]-3-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-propyl}-carbamic acid tert-butyl ester. [MH]+ 553.0.

Provenance & Evidence