O-[(Ethoxycarbonyl)cyanomethylenamino]-N,N,N',N'-tetramethyluronium Hexafluorophosphate

Experimental procedure: HOTU (0.25 mmol) is added to a mixture of Cbz-Phe-OH (0.25 mmol), H-Ala-OCH₃·HCl (0.25 mmol) and N-methylmorpholine (0.75 mmol) in dry acetonitrile (5 mL) at 0 °C. The reaction mixture is stirred at the same temperature for 1 h and then at room temperature for 2 h. EtOAc (50 mL) is added and the mixture is subsequently washed with 10% aqueous HCl (v/v), saturated aqueous Na₂CO₃ and saturated aqueous NaCl solution (2 × 10 mL). Finally, the organic solvent is dried with anhydrous Na₂SO₄, filtered, and the solvent is removed under reduced pressure. The gummy residue is dried under vacuum to obtain 1 (> 99% yield, DL < 1%).