4-Methylmorpholine → methyl Boc-L-tyrosyl-D-methionyl-glycyl-L-phenylalanyl-3-amino-1-adamantanecarboxylate

Participants

Reaction Conditions

Reaction Steps

5.06 Grams of Boc-L-tyrosyl-D-methionyl-glycine is dissolved in 40 ml of dimethylformamide and 1.28 ml of N-methylmorpholine is added to the solution. The reaction mixture is cooled to -50° C. and 1.51 ml of isobutylchloroformate is added causing a precipitate to form. The reaction mixture is allowed to warm to -20° over a 15 minute period and 4.45 g of methyl L-phenylalanyl-3-amino-1-adamantanecarboxylate hydrochloride is added followed immediately by 1.25 ml of N-methylmorpholine The gum which forms dissolves in about 45 minutes while warming to room temperature. The reaction mixture is allowed to stand for 1.5 hours at room temperature and is then stored at 5° C. for 3 days. The reaction mixture is warmed to room temperature, 1.0 ml of N,N-dimethylethylenediamine is added and the reaction mixture is stirred for 10 minutes. The dimethylformamide is removed under reduced pressure at 32° C. and the residue is dissolved in a mixture of 70 ml of water and 100 ml of ethyl acetate. The aqueous layer is separated and extracted once with ethyl acetate and the combined ethyl acetate solutions are washed three times with 70 ml of a 0.5 M solution of potassium bisulfate, once with 70 ml of water, two times with a 0.5 M solution of potassium carbonate, and three times with 70 ml of a 10% sodium sulfate solution, then dried over magnesium sulfate. The solvent is removed under reduced pressure to give the crude product which is then purified by low pressure chromatography on silica gel to give methyl Boc-L-tyrosyl-D-methionyl-glycyl-L-phenylalanyl-3-amino-1-adamantanecarboxylate which is represented by the following formula ##STR25##

Provenance & Evidence