Ethyl - 3-hydroxybutyrate

Figure 4.3 Continuous stripping synthesis of (R)-ethyl-3-hydroxybutyrate from ethyl acetoacetate applying a stirred-tank reactor, stripping module, extraction module and distillation...

Ethyl acetoacetate Ethanol Horn 24 Ethyl 3-hydroxybutyrate (100) 4.2... 

Other classes of alcohols are unreactive. Ethyl 3-hydroxybutyrate (a p-hydroxy ester) went to the phosphate stage, but would not undergo azide displacement. In this example about 30% of the crotonate was formed because of p-elimination. 

G. Guanti, L. Banfi, E. Narisano, and R. Riva, Stereoselective synthesis of W-acetyl-L-lolyposamine from (S) ethyl (3-hydroxybutyrate, Tetrahedron Lett. 33 2221 (1992). 

Ethyl 3-hydroxybutyrate (pg L x) Diethyl succinate (pg L ) Isoamyl acetate (pg L )... 

The / -keto esters are reduced to the respective chiral ft -hydroxy esters by at least two alternative enzymes one of which is D-directing the other one is L-directing (Fig. 3.4). A product mixture results that contains both enantiomeric forms, d and i.,b of the carbinol (/1-hydroxy ester) in varying degrees. In the case of ethyl acetoacetate (1) preferably the L-form of ethyl 3-hydroxybutyrate (l-4) is produced which is then secreted from the cell [55-58]. The L-directing enzyme is methyl butyralde-hyde reductase (MBAR EC 1.1.1.265), and the D-enantiomer is formed by the action of /J-ketoacyl reductase (KAR EC 1.1.1.100) which is a constituent of fatty acid anabolism (Fig. 3.4) [49, 59]. Alcohol dehydrogenase (ADH EC 1.1.1.1) L-directing activity is classically attributed to was shown to be inactive - moreover the enzyme is even inhibited by the substrate [2, 34, 37]. 

Over Ni-kieselguhr (eq. 5.35, A),121 copper-chromium oxide (eq. 5.35, B)7 and Raney Ni (eq. 5.35, C)122 in ethanol, ethyl acetoacetate is hydrogenated quantitatively to ethyl 3-hydroxybutyrate under the conditions described in eq. 5.35. 

However, over Ni-kieselguhr in the absence of solvent or in ether and methylcyclo-hexane 32-33% of a diester, ethyl 3-(3 -hydroxybutyryloxy)butyrate (8), was produced along with 68-67% of ethyl 3-hydroxybutyrate and small quantities of dehydroacetic acid, and over copper-chromium oxide 16% of the diester and 7% of dehydroacetic acid were formed in the absence of solvent. It was suggested that the diester is formed through the hydrogenation of the intermediate 9, which results from 2 mol of acetoacetic ester with elimination of 1 mol of ethanol and that the condensation reaction is reversible (Scheme 5.6). Hence, the formation of the diester is depressed in the hydrogenation in ethanol.121 The reaction pathway in Scheme 5.6 has... 

A reactor was charged with ethyl-3-hydroxybutyrate (194.0 g), cyanoacetic acid (149.83 g), 4-dimethylaminopyridine (10.76 g), and 1500 ml of CH2CI2 and then treated with 75 ml of DMF. The solution was chilled in an ice-water bath and treated with dicyclohexylcarbodiimide (363.45 g) dissolved in 600ml of CH2CI2. A white precipitate formed within five minutes after the start of the addition, and the mixture was stirred overnight. The precipitate was then removed by filtration and the filtrate concentrated. The product was isolated in 73% yield after being distilled twice under vacuum, bp= 100-109°C/0.20-0.27mmHg. 

Gas Chromatography. System GA—carbromal RI 1513,2-bromo-2-ethylbutyramide RI 1205, 2-bromo-2-ethyl-3-hydroxybutyr-amide RI 1340,2-ethylbutyrylurea RI 1380. 

Acepifylline Fluspirilene 1340 2-Bromo-2-ethyl-3-hydroxybutyr- amide 1547 Acetylcysteine Aminobenzoic Acid... 

Methyl or ethyl acetonacetate can be hydrogenated to (R)- or (5 )-methyl- or ethyl-3-hydroxybutyrate on nickel catalysts. With (/ )- or (5 )-tartaric acid and sodium bromide as promoters, the hydogenation can reach enantiomeric excess (ee) values over 90%. The ee value is defined as the excess of the major enantiomer to the minor one over the total yields. The products are vitamin precursors. The function of tartaric acid is believed to form nickel(II) tartarate, which is adsorbed on the metal surface. The asymmetric site... 

New syntheses of ( + )- and (-)-320 from optically active ethyl 3-hydroxybutyrate, which led to grandisols of higher rotations than the published values, have been described by Mori (K. Mori, personal communication. 

Reaction of the lithium enolate of ethyl (3-hydroxybutyrate with trisyl azide furnishes the azide in 77% yield but with only 64% anti diastereomeric excess the diazo ester (10%) and the diazide (1%) are also formed.318... 

Condensation reactions between the lithium dianion of (S)-ethyl 3-hydroxybutyrate (127 R = OH) and cinnamaldimine (128), in connection with the synthesis of thienamycin, have been reported independently by three groups Georg et Cainelli et a/. " and Hart and Ha. Their results are summarized in Scheme 27 and Table 17 (entries 1-3) analogous reactions of dianion (127) with A -silylimines are discussed in Section 4.1.3.3.1. Of the four possible diastereomeric 3-lactams (129)-(132) that can be produced in this reaction, the two that prevail, (129) and (130), contain the predicted relative stereochemistry at C-3 and C-T. Subsequent inversion of the hydroxy groups of (129) and (130) led to intermediates which constituted formal total syntheses of thienamycin. " " In addition to 3-lactams (129) and (130), trans 3-lactam (131) is sometimes isolated but cis 3-lactam (132) is never observed. The product distributions are not uniform and may reflect the different bases used or the rate at... 

We will focus here on a simple hydroxylation process of enolate radicals generated from ester enolates via SET oxidation. Ferrocenium ion was used as the oxidizing agent, and the radical intermediate was trapped with TEMPO [48]. In a second step, the alkoxylamine was reduced with zinc to the corresponding a-hydroxyester. The hydroxylation of ethyl 3-hydroxybutyrate gave the ethyl 2,3-dihydroxybutyrate with moderate stereocontrol (Scheme 17). 

A mild and inexpensive way to reduce aldehydes or ketones uses fermenting Baker s yeast. This is a whole-cell system that contains oxidoreductase enzymes and cofactors that reduce the substrate. The ketonic carbonyl groups of (3-keto-esters and cyclic ketones are reduced with high selectivity using Baker s yeast. Typical in this regard is the reduction of ethyl acetoacetate, which gives ethyl 3-hydroxybutyrate as predominantly the (5)-stereoisomer (7.101). Similarly, the ketone 114 gave the optically active 3-hydroxyproline derivative 115 (7.102). 

Figure 5.3. Effect of loading of Ru on enantioselectivity in the hydrogenation of ethyl acetoacetate into ethyl 3-hydroxybutyrate over Ru-silica catalysts modified with (2R,3R)-tartaric acid (reduction time 0.5 (upper curve) or 5 h (lower curve) crystallite sizes after 0.5h reduction time were 1.6 nm (at 1.5% Ru), 4.5 nm (at 4.2% Ru) or 8 nm (at 11.5% Ru) (according to Vedenyapin et al. ).

Another problem hindering true evaluation of the role of crystallinity of metal catalyst consists of the inhibition effect of the product. Namely, the predominant product of the reaction, (/ )-(-)-3-hydroxybutyrate, can decrease enantioselectivity of the reaction owing to the fact that the relative adsorption coefficient of the (-)-enantiomer on modified chiral Ni centers is somewhat larger than those of the racemic product, (found by Chernyshova et al. and by Neupokoev et al. Therefore, introducing (i )-(-)-ethyl 3-hydroxybutyrate (EHB) into the reaction mixture of ethyl acetoacetate(EAA)or (-)-methyl3-hydroxybutirate (MHB) into the reaction mixture of methyl acetoacetate... 

Although most synthetic approaches to L-daunosamine start from carbohydrate precursors, some routes employ chiral synthons derived from other sources. The aldehydes 213 obtained through reaction of cinnamaldehyde with acetaldehyde in the presence of Baker s yeast followed by ozonolysis [157], and 214 obtained from L-tartaric acid [158-160] have been utilised in the synthesis of daunosamine derivatives, and protected daunosamines and acosamines have been synthesised from (synthetic approaches have employed lactic acid as a chiral starting material [162, 163] and the (S)-amine 215 obtained by resolution has been converted to V-benzoyl daunosamine together with its 3-epimer [164]. Wovkulich and Uskokovic have... 

Butanoic acid, 3-hydroxy-, ethyl ester. See Ethyl 3-hydroxybutyrate Butanoic acid, 2-methyl-. See 2-Methyl butyric acid... 

Ethyl hydrosulfide. See Ethyl mercaptan Ethyl hydroxide. See Alcohol Ethyl 2-hydroxybenzoate. See Ethyl salicylate Ethyl 4-hydroxybenzoate. See Ethylparaben Ethyl-o-hydroxybenzoate. See Ethyl salicylate Ethyl p-hydroxybenzoate. See Ethylparaben Ethyl-4-hydroxybenzoate potassium salt. See Potassium ethylparaben Ethyl 3-hydroxybutanoate. See Ethyl 3-hydroxybutyrate Ethyl 3-hydroxybutyrate CAS 5405-41-4 EINECS/ELINCS 226-456-2 FEMA 3428... 

---