Triethylamine → O-Benzyl-N-(tert-butoxycarbonyl)-L-tyrosyl-Nepsilon-benzyloxycarbonyl-L-lysine methyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of 1.04 g (2.64 mmol) of Nε -benzyloxycarbonyl-Nα -(tert-butoxycarbonyl)-L-lysine methyl ester in 5.3 mL of trifluoroacetic acid was stirred for 2 hours at room temperature. The reaction mixture was evaporated in vacuo to give a colorless oil, which was mixed with 0.966 g (2.6 mmol) of O-benzyl-N-(tert-butoxycarbonyl)-L-tyrosine, 0.37 mL (2.6 mmol) of triethylamine and 20.8 mL of chloroform. To that mixture was added, in one portion, 0.54 g (2.6 mL) of dicyclohexylcarbodiimide at 0° C. The reaction mixture was stirred for one hour at 0° C. and then overnight at room temperature. The solvent was removed by evaporation and the residue was chromatographed on silica gel, using first methylene chloride and then 1:1 methylene chloride/ethyl acetate as eluents, to give 0.49 g (29.1%) of a colorless solid. NMR (CDCl3) δ 7.3 (10 H, m), 7.1 (2H, d), 6.85 (2H, d), 6.5 (1H, m), 5.1 (2H, s), 5.0 (1H, m), 4.7-4.1 (2H, m), 3.65 (3H, s), 3.3-2.9 (4H, m), 1.4 (9H, s). A portion of the product was recrystallized from a mixture of ethyl acetate and isopropyl ether to give crystals melting at 167°-168° C. The product has the formula ##STR118## as confirmed by elemental analysis.

Provenance & Evidence