Dimethylformamide → Nalpha-benzyloxycarbonyl-L-glutaminyl-L-tryptophan methyl ester

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Reaction Steps

To a stirred mixture of Nα -benzyloxycarbonyl-L-glutamine, 56 g., and L-tryptophan methyl ester hydrochloride, 56 g., in 300 ml. of dimethylformamide at 5° C. is added diphenylphosphorazidate, 47.5 ml., in 100 ml. of dimethylformamide dropwise over ten minutes followed by 61.6 ml. of triethylamine over one hour. The mixture is stirred in an ice bath for three hours and at room temperature for 18 hours. After evaporation the residue is dissolved in 1 l. of ethyl acetate and washed successively with 500 ml. of 1N hydrogen chloride solution, 500 ml. of a saturated solution of sodium bicarbonate and 500 ml. water. The ethyl acetate layer is separated, dried, evaporated and 74.2 g. of Nα -benzyloxycarbonyl-L-glutaminyl-L-tryptophan methyl ester is obtained by recrystallization from methanol; m.p. 197°-198° C.

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