Butyric esters, synthesis from

Methylheptanoic acid has been prepared by mixed electrolysis of / -methylglutaric acid monomethyl ester and butyric acid, followed by saponification of the methyl ester,10 and by the mal-onic ester synthesis from 2-bromohexane.11 The present method7 has the advantage of avoiding the use of secondary bromides, which are often difficult to secure entirely pure.12... 

The resolution of racemic FTC butyrate (34) was required for the synthesis of the antiviral drug emtricitabine (Emtriva) (Scheme 7.15) a nucleoside reverse transcriptase inhibitor targeted for treatment of human immunodeficiency virus (HIV) and hepatitis infections [35]. The racemic FTC butyrate ester (34) was treated with immobilized cholesterol esterase, which cleaved the required isomer to the corresponding alcohol (-) 35 with 91% and 52% conversion [36]. The product was isolated as the hydrochloride salt to give 31% yield (98% ) from the 8 kg demonstration. The esterase was immobilized by precipitation onto an accurel polypropylene support using acetone followed by cross linking with glutaralde-... 

Carnitine, L-3-hydroxy-4-(trimethylammonium)butyrate, is a water-soluble, tri-methylammonium derivative of y-amino-jS-hydroxybutyric acid, which is formed from trimethyllysine via y-butyrobetaine [40]. About 75% of carnitine is obtained from dietary intake of meat, fish, and dairy products containing proteins with trimethyllysine residues. Under normal conditions, endogenous synthesis from lysine and methionine plays a minor role, but can be stimulated by a diet low in carnitine. Carnitine is not further metabolized and is excreted in urine and bile as free carnitine or as conjugated carnitine esters [1, 41, 42]. Adequate intracellular levels of carnitine are therefore maintained by mechanisms that modulate dietary intake, endogenous synthesis, reabsorption, and cellular uptake. 

The sodiomalonic ester synthesis was used in the preparation of /3-(quinuclid-2-yl)propionic acid (95) starting from 2-bromomethyl-quinuclidine,128 and y-(quinuclid-3-yl)butyric acid from 3-(j9-chloro-ethyl)quinuclidine.125... 

Among the ether acids prepared by the malonic ester synthesis are 6-phenoxycaproii. acid (65% over-all) from S-phenoxybutyl bromide ana y-(o-anisyl)-butyric acid (80%) from /3-(o-anisyl)-ethyl bromide/ ... 

As already indicated, a special problem with esters is their preparation from two natural precursor molecules by a chemical ester synthesis. Such products have to be labelled nature-identical. For an interesting positional H-NMR study on ethyl butyrate from enzymatic esterification of beet ethanol with butyric acid from milk see [317]. Another chance to detect a corresponding adulteration would be a positional carbon and oxygen isotope analysis of the ester components. Isotope effects on the esterification reaction in question seem to influence characteristically the 8-values of the atoms involved, and hence form a basis for the origin assignment of these compounds (for further details see 6.2.2.4.4). 

Seebach completed the first synthesis of optically active 9 as depicted in Scheme 4.2. ° Protected alcohol 10, available from an optically active p-hydroxy butyric ester, was alkylated with 2-lithio-1,3-dithiane. Deprotonation of this material followed by formylation with DMF then afforded 11. Chain extension to the unsaturated ester was accomplished via a Wittig condensation and deprotection to produce the monomeric unit 12 in 57% overall yield from 10. Double lactonization under Mitsunobu conditions (DEAD-PhjP) afforded a 60%... 

Esters made from unsaturated alcohols usually react smoothly with synthesis gas vinyl acetate gave 30% a-acetoxypropionaldehyde together with 22% of the p-isomer [24], and allyl acetate produced a-acetoxy-butyr-aldehyde in 75% yield [24]. Under certain conditions, it is possible to split out the acid group and obtain the unsaturated aldehyde [272]. 

A useful synthesis of 2-piperidones from 3-substituted butyric esters, aldehydes, and amines in acetic acid has been reported. Yields vary, and the reactions are best... 

Labeled a-bromomethyl derivatives can be prepared from the ketones by treatment with pyridinium tribromide elementary bromine, or CuBr2. One example of the preparation and use of such intermediates is the extension of the aliphatic side chain by two carbon atoms using the malonic ester synthesis to produce the 4-aryl-4-oxo[4- C]butyrate (7) in good yield (Figure 6.7). 

Tetrahydropyran-2-methanol and tetrahydrofurfuryl alcohol are key chiral intermediates for the synthesis of polyether antibiotics. Such antibiotics are known as ionophores, which are able to transport metal ions across biological membranes. Some of their medicinal applications are in diuretics and analgesics [211]. Chiral (S)-tetrahydropyran-2-methanol 119 and 120 has been prepared from the hydrolysis of its butyrate ester 121 using porcine pancreatic lipase [212]. The unreacted (R) enantiomer of ester 122 was hydrolyzed by lipase from Candida rugosa. Both enantiomers were prepared in more than 97% e.e. (Fig. 42). 

Tetracaine Tetracaine, the 2-diethylaminoethyl ester of 4-butylaminobenzoic acid (2.1.6), is also structurally analogous to procaine, in which the amino group of the benzene ring is replaced by a butylamine radical. The methods for its synthesis are the same as the above-mentioned methods for procaine or chloroprocaine, with the exception of using 4-butylaminobenzoic acid in place of 4-aminobenzoic acid. There is also a proposed method of synthesis that comes directly from procaine (2.1.1). It consists on its direct reaction with butyric aldehyde and simultaneous reduction by hydrogen using a palladium on carbon catalyst [6]. 

The enzyme-catalyzed production of (R)-2-(2-aminobutyl)-3-chlorothio-phene ((R)-42) was a research project at Zeneca a few years ago [72]. Compound 42 was an intermediate in the preparation of adenosine derivatives and Scheme 13 outlines the relevant enzymatic step. Racemic alcohol rac-40 was treated with Rhizomucor miehei lipase immobilized on an ion-exchange resin (Lipozyme RM IM from Novozymes) in the presence of vinyl butyrate to yield the free (S)-alcohol 40 and the (R)-ester 41. Alcohol 40 was subsequently converted into the strategic intermediate 42, which found further use in the synthesis of antihypertension drugs. 

In this way they prepared butyric ethyl ester from potassium acetate and potassium-ethyl succinate. The synthesis of the ethyl ester of valeric, capronic, and isobutyl-acetic acid was also effected. 

The large-scale industrial synthesis of organic cellulose esters is practically restricted to the production of esters from a few aliphatic fatty acids with up to four carbon atoms, namely cellulose acetate (CA), cellulose acetate propionate (CAP), and cellulose acetate butyrate (CAB) [22], Typical degrees of substitution for plastic moulding compounds are presented in Table 3.1 with data calculated from ref. [22],... 

In 1865 Frankland and Duppa reported the synthesis of butyric and caproic esters by the action of sodium, followed by ethyl iodide, on ethyl acetate, mentioning in a footnote that they had become aware of the work of Geuther (see below). They point out that butyric and caproic esters are formed by substitution from acetic ester in the first reaction they supposed that one hydrogen atom in the methyl group of acetic ester was replaced by sodium and in the second reaction two atoms, and that by the action of ethyl iodide the esters of butyric and caproic acids were obtained. In this paper type formulae alone are used, equivalent to ... 

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