Acetic hydrazino-, ethyl ester

The hydrazone link is formed by the reaction of two linkers, J (5,5-dimethoxypentanoic acid, 23) and [l-(9-fluorenylmethoxycarbonyl)-2-(isopropylidene)hydrazino]acetic add (25). J (23) is obtained by hydrolyzing the corresponding methyl ester, which is commercially available or can be prepared by following the method of Stevens and Lee1 43 (Scheme 11). Compound 25 is prepared by protecting commercially available ethyl hydrazinoacetate hydrochloride (24) (Scheme 12)J1211... 

Synthesis of 4-amino-2-pyrazolin-5-ones is usually achieved by treatment of an a-amido-/3-aldehydo- or /9-ketoester with hydrazines according to the classical method for preparation of 2-pyrazolin-5-ones. Variants on this procedure consist of using an a-amidoester which has /9-substituents whose reaction is equivalent to that of a /9-carbonyl substituent. Such compounds are D-benzylpenicilloic acid a-methyl ester,1027 ethyl phenylpenaldate243 and the acetal of an a-amido-/9-formyl ester.59,243 Cornforth has isomerized 2-phenyl-4-hydrazino-methylidyneoxazolidone to 4-benzamido-2-pyrazolin-5-one. The same compound was obtained by treatment of 1-ethoxyvinyl-2-phenyl-oxazolidone with phenylhydrazine.319... 

From ethyl 2-cyanoacetate. 5-Aminopyrazol-3-ones can be conveniently prepared from /7-keto esters with hydrazines. Thus, heating ethyl 2-cyanoacetate 142 with (4-ferf-butylphenyl)hydrazine 143 in ethanolic sodium ethoxide afforded 5-amino-2-(4-ferf-butylphenyl)-2,4-dihydropyrazol-3-one 144 (01JMC3730) (Scheme 33). The reaction that takes place under acidic conditions, between ethyl 2-cyanoacetate 142 and 2-hydrazino-6-oxopyrimidine-5-carbonitrile 145 in boiling acetic... 

Sato and Noyori published two syntheses for homopyrazofurin (311) (79H141 83BCJ2700), the most recent of which used the C-glycosylpyruvic ester 181 (Section VI,C Scheme 34), which reacted with ethyl hydrazino-acetate to give 310 followed by ammonolysis and deprotection to 311 (Scheme 68). 

Ethyl N-benzyl-L-phenylalaninate treated 0.5 hr. at 80° with 1.2 equivalents NaNOg in 2 equivalents 1N HCl N-nitroso deriv. (Y ca. 100%) treated with Zn-dust in 3 1 acetic acid-acetic anhydride N -acetyl-Na-benzyl-L-a-hydrazino ester (Y 80%) hydrogenated with 5%-Pd-C in ethanol containing p-toluenesulfonic acid debenzylated compd. (Y 85%) heated 0.5 hr. at 110° in 6 N HCl under Ng L-a-hydrazino-j -phenylpropionic acid (Y 87%). F. e. s. K. Achiwa and S. Yamada, Tetrah. Let. 1975, 2701. 

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