4-Methylmorpholine → Acetylprolylalanylprolyl-2-azaalanyllactyllactic acid ethyl ester

Participants

Reaction Steps

A mixture of 0.00185 moles of acetylprolylalanylproline and 0.20 ml of N-methylmorpholine in 20 ml of acetonitrile is cooled to -20° by means of a Dry Ice acetone bath. To this is added 0.28 ml of isobutyl chloroformate. After stirring for 10 minutes at -20° there is added 0.00185 moles of 2-azaalanyllactyllactic acid ethyl ester in 5 ml of acetonitrile. The reaction mixture is allowed to warm to room temperature after which it is stirred for 2 hours and then concentrated in vacuo. The residue is extracted between 50 ml of methylene chloride and 20 ml of cold 0.25 N hydrochloric acid. The acid layer is backwashed 2 times with 25 ml of methylene chloride. The organic extracts are combined, dried over sodium sulfate and concentrated in vacuo to give a glass. This residue is chromatographed on 75 gm of silica gel. Elution with methanol/methylene chloride (1-4%) gives pure acetylprolylalanylprolyl-2-azaalanyllactyllactic acid ethyl ester.

Provenance & Evidence