4-Methylmorpholine → N,N'-Dicyclohexylurea

Participants

Reaction Steps

To a solution of freshly prepared acetonide-protected amino acid (0.2 mmol, 1 equiv) in acetone (1.5 mL) was added 3 mL of THF, N-methylmorpholine (0.22 mmol, 1.1 equiv), 1-hydroxybenzotriazole (0.44 mmol, 2.2 equiv), and hexapeptide amine (0.22 mmol, 1.1 equiv). The resultant mixture was cooled to 0° C. and DCC (0.22 mmol, 1.1 equiv) was added. The mixture was allowed to warm up to room temperature and stirred under N2 for 20 h, after which time the precipitated dicyclohexylurea (DCU) was removed by filtration and washed with small portion of CH2Cl2. The combined filtrate was washed with saturated NaHCO3 solution and dried over MgSO4. Concentration in vacuo and dissolution of the residue in EtOAc yielded more DCU. The residue remaining after a second filtration and concentration in vacuo was purified by chromatography with 10-40% acetone in freshly distilled n-hexane to give the N,O-Isopropylidene-protected heptapeptide 1-7 (SEQ ID NO:10).

Provenance & Evidence