Ethyl acetamidocyanoacetate

The oxazolidine-2,5-dione heterocycle, perhaps better known as the N-carboxyanhydride of an amino acid, has been incorporated employing a modification of chloromethylated poly(styrene) (192) (76USP3985715). The reaction sequence involved utilization of a masked amino acid, ethyl acetamidocyanoacetate (205). The amino acid was liberated in a subsequent hydrolysis/decarboxylation step (Scheme 98). The cyclized, IV-carboxyanhydride-functional resins (206) were reported to be useful in solid phase peptide synthesis and as supports for enzyme immobilization. 

Method Two, Albertson and iHillar (50). j3-methylthiolethanol is prepared in 80% yield from monothioethylene glycol and dimethylsulfate. This product is chlorinated by action of thionyl chloride or HCl, and the intermediate, j8-methylthiolethyl chloride, is condensed in solution with ethyl acetamidocyanoacetate to give a 60% yrield of ethyl o-aoetamido-o-cyano-Y-methylthiolbutyrate. The latter is hydrolyzed with base to give 80% yield of recrystallized DL-methionine. The over-all yield of product is about 48%. 

Method Six, Albertson and Tullar (50). Ethyl- -acetamido-flt-cyano-j3-phenylpropionate (A) is prepared in 83% yield from benzyl chloride and ethyl acetamidocyanoacetate . DL-Phenylalanine is prepared in see p. 369, 860 , see p. 361. 

Synthesis. DL-Tryptophan is synthesized in 70% over-all yield from crude indole by the method of Albertson and Tullar (50). Ethyl o-acetamido-a-cyano-/3-(3-indolyl)-propionate (A) is prepared in 98% yield from ethyl acetamidocyanoacetate , gramine (3-dimethylamino-methyl indole) , sodium, ethanol and ethyl iodide according to the procedure described by Albertson et al. (49). OL-Tryptophan is prepared by alkaline hydrolysis of (A). Other practicable syntheses of tryptophan which have been reported recently are outlined in the following equations. 

---