Hydrolysis with sodiomalonic ester

The above method is adapted from the procedure of Day and Thorpe.1 /3-Methylglutaric acid has been prepared by hydrolysis of jS-methylglutaronitrile 2 by condensation of crotonic ester with ethyl sodiocyanoacetate, and with sodiomalonic ester 3 4 and by condensation of acetaldehyde with malonic ester. ... 

More recently. Prelog (194) has described an ingenious synthesis of quinuclidine, also adapted to the preparation of 2-ethylquinuclidine (195), which empiloys tetrahydropyranol (CLII) (196) as starting material. The substance was first converted into the corresponding benzene-sulfonyl derivative (CLIII), which was then treated with sodiomalonic ester. Hydrolysis and decarboxylation of the resulting substituted malonate afforded tetrahydropyranyl-4-acetic acid (CLIV). Bouveault... 

The introduction of a side chain at C13 was studied by Wilds [186, 188] (Scheme 6). Alkylation of the ketone (53) with bromoac.etic ester and saponification led to the acid (55). The latter was converted into the methyl ketone (58) by condensing its chloride with sodiomalonic ester, hydrolysis. 

The main starting material for the majority of syntheses of these compounds is )S-(m-anisyl)ethyl bromide (78), obtained in ten stages from m-aminophenol with an over-all yield of 22% [209]. The successive condensation of the bromide (78) with sodiomalonic ester and the chloride of glutaric semiester led to the keto triester (79), which by cyclization, saponification, and methylation was converted into the bicyclic diester (80) [188, 209]. In another variant, the bromide (78) was condensed with the diester of p -oxo-pimelic acid to form the keto diester (73) from which the diester (80) was again obtained by cyclization, hydrolysis, and methylation [210]. 

A longer route for the synthesis of equilenin derivatives [278] consists in the successive condensation of the bromide (3) with sodiomalonic ester and the half-chloride of succinic acid. The ketotriester (162) obtained is cyclized into the tricyclic triester (163), which, on hydrogenation, saponification, and decarboxylation, gives the diacid (164). The cyclization of its anisyl ester with subsequent acid hydrolysis leads to 18-norequilenin (165), identical with the product obtained by a total synthesis of the AB D C type (Scheme 31). 

Aminobutyric acid has been prepared by the electrolytic reduction of succinimide to pyrrolidone and hydrolysis of the latter by means of barium hydroxide,1 by the oxidation of piperylurethan with fuming nitric acid and the treatment of the resulting product with concentrated hydrochloric acid in sealed tubes at 100°,3 and by the hydrolysis of the condensation product from 2V-(/3-bromoethyl)-phthalimide and sodiomalonic ester.4 The present method is a slight modification of that of Gabriel.2... 

Two variations of the malonic ester synthesis make use of dihaloalkanes. In the first of these, two molar equivalents of sodiomalonic ester are allowed to react with a dihaloalkane. Two consecutive alkylations occur, giving a tetraester hydrolysis and decarboxylation of the tetraester yield a dicarboxylic acid. An example is the synthesis of glutaric acid ... 

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