Alkylation of esters

Direct alkylation of esters can be carried out by forming the enolate with LDA fol lowed by addition of an alkyl halide Tetrahydrofuran (THF) is the solvent most often used m these reactions... 

It is also possible to fill the last place in an otherwise blocked carbonyl compound since further alkylation is impossib-le and the molecule is too crowded to condense with itself. Again strong bases are needed, such as PhgC used in the alkylation of ester (10). 

Scheme 1.6 gives some examples of alkylation of esters, amides, and nitriles. Entries 1 and 2 are representative ester alkylations involving low-temperature... 

Preparation of the quaternary anticholinergic agent benzilonium bromide (47) is begun by conjugate addition of ethylamine to methylacrylate, giving aminoester 42. Alkylation of 42 with methyl bromo-acetate leads to diester 43, which is transformed into pyrrolidone 44 by Dieckmann cyclization, followed by decarboxylation. Reduction of 44 by lithium aluminum hydride leads to the corresponding amino-alcohol (45). Transesterification of alcohol 45 with methyl benzilate leads to 46. Benzilonium bromide (47) is obtained by alkylation of ester 46 with ethyl bromide. 2... 

Scheme 1.9. Alkylation of Esters, Amides, Imides and Nitriles... 

Alkylations of esters, in which the a-carbon atom is not part of a ring and in which there is no heteroatom substituent in the carbon chain, have not been studied systematically, for the reason that a low degree of diastereoselection is expected. 

Table 7. Formation of Six-Membered Rings by Intramolecular Alkylation of Ester Enolates...

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