2-Bromo-3-hydroxybutyric acid

Bromo-3-hydroxybutyric acid is obtained by passing a stream of air laden with bromine into a rapidly stirred aqueous 0.34m-solution of crotonic acid.284... 

Disposition in the Body. Readily absorbed after oral administration. The major metabolite is free bromide ion hydrolysis to an active metabolite, 2-bromo-2-ethylbutyramide, also occurs followed by oxidation to 2-bromo-2-ethyl-3-hydroxybutyramide other metabolites include 2-ethylbutyrylurea and 2-ethyl-2-hydroxybutyric acid. Carbromal is excreted in the urine mainly as bromide ion and partly as 2-ethyl-2-hydroxybutyric acid, with very little as unchanged drug. Peak bromide excretion is attained after about 48 hours. 

The 3(R)-hydroxybutyric acid and its a-bromo derivative have also been utilized in such acid halide-imine methodology to produce optically active P-lactams of type 72 and 73 [5g]. However, with few exceptions the yields in the cycloaddition step with imines derived from glyoxals and glyoxilic esters were low [5g]. 

Intramolecular nucleophilic substitution by an active methylene linked to the nitrogen atom of a-substituted carboxamides was first utilized in azetidinone synthesis by Sheehan and Bose in 1950 [27]. When 3-hydroxyethylazetidinones became an important research target, it was realized that L-threonine or D-allo-treonine, easily converted to bromohydrins 57,61 or to epoxyacid 64, are by this method one of the most convenient natural chiral source for penem and carbapenem synthesis. Shiozaki et al. [28] at Sankyo s laid down the fundaments of the threonine route . Early works from D-a//o-threonine-derived 2R-bromo-3R-hydroxybutyric acid 57 were run using malonate anions as the nucleophilic moiety, as shown in amide 58, which in presence of DBN cyclized to azetidinone 59a with complete inversion of configuration [28a, c]. 

Melikow, Ann., 1886, 284, 207. l-Bromo-2-hydroxybutyric Acid CH3-CH(OH)-CHBr COOH... 

Method Three, Livak et ad. (521). a-Bromo-y-butyrolactone (A) is prepared in 80% yield from y-butyrolactone (commercial avmlable), FBr, and bromine. a-Amino-y-hydroxybutyric acid (B) is prepared in 60% yield by amination of (A). 5-()8-Bromoethyl)-hydantoin (C) is prepared in 51% yield by the reaction of (B) with potassium cyanate to give y-hydroxy-a-ureidobutyric acid (D) and by the HBr hydrolyris of (D). 5-(j0-Methylmercaptoethyl)-hydantoin (E) is prepared in 73% yield from sodium methylmercaptide and (C). DL-Methionine is prepared in 95% yield by the Ba(OH)j hydrolysis of (E). The over-all yield is about 17%. 

A first group of ISPR systems, most commonly with reductions, is those using the addition of a resin or porous adsorbent to remove the product. Early work on ketone reduction showed already that hydrolysis and also loss of ee could be overcome by maintaining low concentrations of the substrate in the reaction. One successful approach involves the controlled release of the substrate from a resin placed in the reaction media. For example, Amberlite XAD-2 resin enhanced the asymmetric reduction of ethyl 4-chloroacetoacetate to (S)-4hydroxybutyric acid ethyl ester catalyzed by yeast [34]. In the subsequent development of the technolt, the approach was extended to simultaneous substrate supply and product removal. A similar approach was developed for the asymmetric reduction of 6-bromo-P-tetralone [35]. 

To this end, several routes passing through the known (S)-methyl-4-bromo-3-hydroxybutyrate 26, an intermediate used m prior syntheses of HMGRIs, were developed. This key intermediate was derived most efficiently from isoascorbic acid as shown in Scheme 5. Protection of 26 as the f-butyl-dimethylsilylether, followed by conversion to the nitnle provided an advanced intermediate (27) that could be taken in several directions. 

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

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