3-Oxobutanoate esters, acidity

Methyl 3,3-dimethyl-4-oxobutanoate Butanoic acid, 3,3-dimethyl-4-oxo-, methyl ester (9) (52398-45-5)... 

Alkyl-substituted 3-oxobutanoic and propanedioic esters can be hydrolyzed under acidic conditions to the corresponding acids, and when these are heated they readily decarboxylate (Section 18-4). Alkyl 3-oxobutanoic esters thus yield methyl alkyl ketones, whereas alkylpropanedioic esters produce carboxylic acids ... 

Ethyl 4-cyclohexyl-4-oxobutanoate Cyclohexanebutanoic acid, Y-oxo-, ethyl ester (9) (54966-52-8)... 

ETHYL 4-CYCLOHEXYL-4-OXOBUTANOATE CYCLOHEXANEBUTANOIC ACID, Y-OXO-, ETHYL ESTER (54966-52-8), 65, 17 ETHYL CYCLOPROPYLPROPIOLATE, 66, 173,174 ETHYL (E,Z)-2,4-DECADIENOATE (3025-30-7), 66, 22, 23, 25, 28 Ethyl 3,4-decadienoate (36186-28-4), 66, 22, 28 Ethyl decanoate Decanoic acid, ethyl ester (110-38-3), 67,125 ETHYL DIETHOXYPROPANOATE PROPANOIC ACID, 3.3-DIETHOXY-,... 

RING EXPANSION AND CLEAVAGE OF SUCCINOIN DERIVATIVES SPIR0[4,5]DECANE-1,4-DIONE AND ETHYL 4-CYCLOHEXYL-4-OXOBUTANOATE (Cyclohexanebutanolc acid.y-oxo-, ethyl ester)... 

Comprehensive work in this field has been done by Slovak authors (98MI1, 95M1359, 96CCC269, 96CCC371, 97CCC99). They prepared 2-substituted (H, Me, Ph) 4-, 5-, 6-, and 7-nitrobenzoxazoles, which were then reduced to amines (not isolated) and subjected to subsequent nucleophilic substitution with activated enol ethers such as alkoxymethylene derivatives of malonic acid esters and nitrile, 3-oxobutanoic acid esters, pentanedione, or cyanoacetic acid esters to yield aminoethylenes 8. 

Ethyl 3-oxobutanoate, commonly called ethyl acetoacetate or ace tome tic ester, is much like malonic ester in that its ct hydrogens are flanked by two carbonyl groups. It is therefore readily converted into its enolate ion, which can be alkylated by reaction with an alkyl halide. A second alkylation can also be carried out if desired, since acetoacetic ester has two acidic a hydrogens. 

The ethyl ester can also be prepared from ethyl acetoacetate (ethyl 3-oxobutanoate) by the method of Rodionov8 as well as via Steinkopf s method.3 Ethyl nitroacetate can be prepared in >70% yields from the dipotassium salt, ethanol, and sulfuric acid, with the addition of anhydrous magnesium sulfate in order to avoid the Nef reaction.9 The propyl and 2-propyl esters can also be obtained by this method. 

Table 12 Asymmetric hydrogenation of 3-oxobutanoic acid esters...

The photo-Fries rearrangement of aryl hydrogen (or methyl) succinates 267 leads to 4-(2-hydroxyaryl)-4-oxobutanoic acids (or methyl esters 268), which are readily cyclized to 5-(2-acetoxyaryl)-2(3//)-furanones (269) (Scheme 68). [189-191] Photolysis of 269 [191] or the analogous open-chain enol acetates [192,193] leads to chromones. 

The most used route to pyridines is called the Hantzsch synthesis. This uses a 1,3-dicarbonyl compound, frequently a 1,3-keto ester [ethyl ace-toacetate (ethyl 3-oxobutanoate)], and an aldehyde, which are heated together with ammonia (Scheme 2.18). At the end of the reaction the dihydropyridine is oxidized to the corresponding pyridine with nitric acid (or another oxidant such as Mn02). The normal Hantzsch procedure leads to symmetrical dihydropyridines. Two different 1,3-dicarbonyl compounds may not be used as two enoiate anions might form, giving mixed products when reacted with the aldehyde. The aldehyde itself should preferably be non-enolizable, otherwise the chance of aldoliza-tion exists, but with care this can be avoided. 

The von Pechmann procedure also works with keto esters. Ethyl ace-toacetate (ethyl 3-oxobutanoate), for example, self-condenses readily in the presence of acid to form ethyl 4,6-dimethylpyran-2-one-5-carboxylate (Scheme 4.8b). 

Disidea Herbacca, obtained the /3-ketoester H2N—CH(iPr)—CO— CH2—COOEt from L-valine. The ester was cyclized to 5-isopropyl-tetramic acid in toluene in the presence of potassium 2-methyl-2-butoxide (84HCA1783). In other cases esters of 4-amino-3-oxobutanoic acid, subsequently cyclized in the presence of base, were synthesized using special heterocycles, such as /3-lactams (91TL3115), imidazoles (91IZV437) or pyrones (89TL3217). (See Fig. 30.)... 

No metalation is required for the / -fluorination of a-oxo esters.150 Ethyl 3-methyl-2-oxo-butanoate and 3-methyl-2-oxopentanoic acid give the corresponding /f-fluoro derivatives 30 a and 30 b, respectively, in quantitative yield on reaction with A-fluorobis(trifluoromethylsul-fonyl)amine (Id). 3-Fluoro-2-oxobutanoic acid (30c) is exclusively formed by treating 2-oxobutanoic acid with an equimolar amount of reagent Id.150... 

The anions of esters such as ethyl 3-oxobutanoate and diethyl propanedioate can be alkylated with alkyl halides. These reactions are important for the synthesis of carboxylic acids and ketones and are similar in character to the alkylation of ketones discussed previously (Section 17-4A). The ester is converted by a strong base to the enolate anion, Equation 18-18, which then is alkylated in an SN2 reaction with the alkyl halide, Equation 18-19. Usually, C-alkylation predominates ... 

Recently, we [67] have described the reduction of the methyl ester of 4-chloro-3-oxobutanoic acid (39) to the methyl ester of S-( )-4-chloro-3-hydroxy-butanoic acid (40) (Fig. 13) by cell suspensions of Geotrichum candidum SC 5469., S ( )-(40) is a key chiral intermediate in the total chemical synthesis of a cholesterol antagonist (SQ 33600), which acts by inhibiting hydroxymethylglu-taryl CoA (HMG CoA) reductase. In the biotransformation process, a reaction... 

Figure 13 Synthesis of chiral synthon for anticholesterol drug SQ 33600 stereoselective microbial reduction of 4-chloro-3-oxobutanoic acid methyl ester (39).

Glucose-grown cells of G. candidum SC 5469 have also catalyzed the stereoselective reduction of ethyl-, isopropyl-, and tertiary-butyl esters of 4-chloro-3-oxobutanoic acid and methyl and ethyl esters of 4-bromo-3-oxobutanoic acid. A reaction yield of >85% and e.e. of >94% were obtained. NAD+-depen-dent oxido-reductase responsible for the stereoselective reduction of P-keto esters of 4-chloro- and 4-bromo-3-oxobutanoic acid was purified 100-fold. The molecular weight of purified enzyme is 950,000. The purified oxido-reductase was immobilized on Eupergit C and used to catalyze the reduction of (39) to S-( - )-(40). The cofactor NAD+ required for the reduction reaction was regenerated by glucose dehydrogenase. 

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