N-tert.-Butyloxycarbonyl-S-

A solution of 3.55 parts of L-tryptophanyl-L-methionyl-L-aspartyl-L-phenylalanine amide trifluoroacetate in 30 parts of dimethylformamide is cooled to 0°C, and 1.01 parts of tri-ethylamine are added. The mixture is stirred while 1.84 parts of N-tert-butyloxycarbonyl-/3-alanine 2,4,5-trichlorophenyl ester are added at 0°C. The reaction mixture is kept at 0°C for 48 hours and then at 20°-23°C for 24 hours. The mixture is added to a mixture of 100 parts of ice-water, 0.37 part of concentrated hydrochloric acid (SG 1.18), 1.2 parts of acetic acid and 20 parts of ethyl acetate. The mixture is stirred for 15 minutes at 0°-10°C and is then filtered. The solid residue is washed with water and then with ethyl acetate, and is dried at 40°-50°C under reduced pressure. There is thus obtained N-tert-butyloxycarbonyl-/S-alanyl-L-tryptophanyl-L-methionyl-L-aspartyl-L-phenylalanine amide, MP 213°C with decomposition. 

A soln. of mercuric chloride in methanol followed by a soln. of Na-acetate trihydrate in the same solvent added to a soln. of N-ferf-butyloxycarbonyl-S-trityl-L-cysteinyl -S-diphenylmethyl-L-cysteinyl -L- alanylglycyl-L-valyl-S- trityl-L-cysteinyl-L-serine methyl ester in dimethylformamide-methanol, and heated gently N- tert - butyloxycarbonyl -S- chloromercuri -L- cysteinyl -S- diphenylmethyl -L-cysteinyl -L- alanylglycyl -l- valyl -S- chloromercuri -L-cysteinyl -L- serine methyl ester (Y 75%) suspended in dimethylformamide, HgS bubbled in, after 1 min. a soln. of Na-acetate trihydrate in methanol added, the introduction of HgS continued for 10 min., and allowed to stand at room temp, for 2 hrs. N-ferf-butyloxycarbonyl - L- cysteinyl -S- diphenylmethyl -l- cysteinyl - l - alanylglycyl -L -valyl-L-cysteinyl-L-serine methyl ester (Y 78%). F. e. and methods s. L. Zervas et al., Am. Soc. 87, 4922 (1965) cf. R. G. Hiskey and J. B. Adams, Jr., J. Org. Ghem. 31, 2178 (1966). 

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