Ethyl glycinate hydrochloride

S g of ethyl glycinate hydrochloride were dissolved in 400 cc of ethanol and 33.5 g of salicylic aldehyde were added. It is refluxed for half an hour and cooled. 38 cc of triethylamlne and 25 g of Raney nickel are then added whereafter hydrogenation is carried out at room temperature and under atmospheric pressure. After hydrogen adsorption was complete, the mixture was filtered and the alcohol evaporated off. The residue was taken up with acidified water, extracted with ether to eliminate part of the by-products, consisting mainly of o-cresol, then made alkaline with ammonia and extracted with ethyl acetate. The solvent was removed in vacuo and the residue crystallized from ether/petroleum ether. 36.7 g of o-hydroxybenzyl-aminoacetlc acid ethyl ester melting at 47°C are obtained. 

The value of using the preformed HHT with diphenyl phosphite in this procedure was readily apparent from the nearly quantitative conversion to glyphosate observed from 25. A much lower yield (38%) of glyphosate was obtained after hydrolysis when the same components (ethyl glycinate hydrochloride and formaldehyde) were mixed and heated with neat triphenyl phosphite to give triester 30 (43). 

The same reagents can be used to form amides from carboxylic acids and amines, a method which is applicable to peptide synthesis. Condensation of A-benzyloxycarbonyl-L-phenylalanine and ethyl glycinate hydrochloride gave an 85% yield of purified dipeptide. 

Ethyiglycinate Hydrochloride Ethyl glycine Hydrochloride,Ethylglycocoll Hydrochloride or Glycine Ethylester Hydrochloride,... 

Ethylglycocoll Hydrochloride. See Ethyl-glycinate hydrochloride in this vol... 

Methyl-3-phenyl-2//-azirinc (21, R = Me) and ethyl glycinate hydrochloride... 

These dienes are transformed into pyrrole esters on treatment with ethyl glycine hydrochloride in hot pyridine, e.g. equation 4566. 

Comforth et al have devised a flexible method of synthesizing oxazoles ( 9) from the condensation of an imino ether (88) and ethyl glycinate hydrochloride, followed by reaction with an alkyl formate and potassium alkoxide, and cyclization of the product in hot acetic acid. The reported yields in various stages are fairly good. 

In some cases, amines can be converted to diazo compounds by treatment with potassium nitrite or nitrous acid. The first aliphatic diazo compound known was ethyl diazoacetate (304), prepared by Curtius in 1883. 41 Treatment of ethyl glycinate hydrochloride (303) with potassium nitrite (KNO2) gave 304. This technique is most useful when an electron withdrawing group is adjacent to the amino group. 

Peptides. 0.017 mole N-carbobenzoxy-DL-alanylglycylhydroxamic acid (prepn. s. 312) dispersed with 0.02 mole ethyl glycinate hydrochloride and 0.02 mole trihutylamine in dry dioxane, stirred and refluxed 5 hrs. until the Fe -test becomes very weak ethyl N-carbobenzoxy-DL-alanylglycylglycinate. Y 76%. F. e. s. E. Hoffmann and I. Faiferman, J. Org. Ghem. 29, 748 (1964). 

A soln. of 2-amino-4,5-dimethylbenzophenone and 1.5 moles of ethyl glycinate hydrochloride refluxed 15 hrs. in pyridine, after 4 hrs. a second portion of ethyl glycinate hydrochloride added, slowly distilled to remove water and alcohol along with pyridine, and fresh pyridine added l,3-dihydro-7,8-di-methyl-5-phenyl-2H-l,4-benzodiazepin-2-one. Y 75%. F. e. and method s. L. H. Sternbach et al., J. Org. Ghem. 27, 3788 (1962). 

Carbobenzoxy-L-phenylalanine N-hydroxyphthalimide ester and ethyl glycinate hydrochloride dissolved in a small amount of dimethylformamide, cooled to ca. —10°, 2 moles of triethylamine added with stirring, and the product isolated after 1 min. ethyl carbobenzoxy-L-phenylalanylglycinate. Y 96%.—N-Hy-droxyphthalimide liberated during the reaction can be easily removed. F. e. s. G. H. L. Nefkens, G. I. Tesser, and R. J. F. Nivard, R. 81, 683 (1962) with N-hydroxysuccinimide esters cf. G. W. Anderson, J. E. Zimmerman, and F. M. Callahan, Am. Soc. 85, 3039 (1963). 

The effect of cetyltrimethylammonium bromide on the rate constants of hydrolysis of ethyl glycinate hydrochloride has been reported. " Cationic and non-ionic micelles inhibited and anionic micelles accelerated the acid hydrolysis of A-p-tolyl-benzohydroxamic acid (189). The rates of acid hydrolysis of acetohydroxamic acid, MeCONHOH, benzohydroxamic acid, PhCONHOH, and A-phenylbenzohydroxamic acid, PhCON(OH)Ph, were increased by perfiuorooctanoic acid and by sodium 1-dodecanesulfonate and sodium dodecyl sulfate (SDS). " The effects of micelles of SDS upon the rates of reaction of ionized phenyl salicylate with Bu"NH2, piperidine and pyrroiidine have been reported. 

Peptides. A mixture of N-benzyloxycarbonyl-L-phenylalanine, ethyl glycinate hydrochloride, triphenylphosphine, bromotridiloromethane, and ethyldiisopropyl-amine refluxed 3 hrs. in tetrahydrofuran ethyl N-benzyloxycarbonyl-L-phenyl-alanylglycinate. Y 85%. F. e. and procedure, also with CCI4 instead of CBrClg, s. L. E. Barstow and V. J. Hruby, J. Org. Chem. 36, 1305 (1971). 

Equimolar amounts of phthaloylglycine and ethyl glycinate hydrochloride treated dropwise with a,a-dichlorodimethyl ether, heated at 100° until HCl-evolution subsides, the resulting methyl formate and excess a,a-dichlorodimethyl ether removed in vacuo -> ethyl phthaloylglycylglycinate. Y 79%. F. e. s. A. Rieche and H. Gross, B. 92, 83 (1959). 

The imidazo[l,2-a]quinoxaline system can also be designed on the basis of compounds that contain neither the quinoxaline ring nor the imidazole ring. In particular, the reaction of compound 176 with ethyl glycinate hydrochloride leads to annulation of the imidazopyrazine system and formation of tetrahydroimidazo-quinoxaline 177 (Scheme 4.77) (Legroux et al. 1987). 

Scheme 4.77 Cyclization of (2-morpholinocyclohex-l-enyl)carbonimidoyl dicyanide when exposed to ethyl glycinate hydrochloride...

O-(N-Benzyloxycarbonylphenylalanyl)pivalohydroxamic acid in acetonitrile added to ethyl glycinate hydrochloride in dimethylformamide, then powdered Na-acetate trihydrate added, and stirred 5 hrs. at room temp. ethyl N-benzyl-oxycarbonylphenylalanylglycinate. Y 88.5%. - No racemization was found. F. e. s. S. Rajappa, K. Nagarajan, and V. S. Iyer, Tetrahedron 23, 4805 (1967) side reactions cf. Tetrahedron 23, 4811. 

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