O Bromopropionic Acid

If an ester of o-bromopropionic acid were desired the appropriate alcohol would now be used, but as the acid itself is required, the bromide is decomposed by addition of one and one-third equivalents of water, the mixture being shaken under a reflux condenser, with a pot of ice close at hand, until homogeneous, and finally warmed for one-half hour on the water-bath. The solution is then cooled, treated with several volumes of ether, dried over sodium sulfate, and concentrated. When fractionated in vacuo the residue boils mainly at 1240 under a pressure of 18-19 mm. and solidifies in a freezing mixture, then melting at about 250. The acid should be protected from the moisture of the air. as it is quite hygroscopic. It is also a powerful skin irritant. The yield should be 60 per cent of the bromide used. 

O -Bromopropionic Acid o-Dibromobenzene p-Dichlorobenzene lodobenzene Nitrobenzene oj-Bromotoluene Guaiacol... 

Similarly, 5-thiazole alkanoic acids and their salts are obtained from thioamides and /3-halo -y-keto acids (695). Thus thioarylamides condensed with 3-aroyl-3-bromopropionic acid (88) in isopropanolic solution in the presence of Na COs give first 4-hydroxy-2-aryl-A-2-thiazoline-5-acetic acid intermediates (89), which were dehydrated in toluene with catalytic amounts of p-toluene sulfonic acid to 2,4-diaryl-5-thiazole acetic acid (90) (Scheme 39) (657), with R = H or Me Ar = Ph, o-, m- or p-tolyl, o-, m-, or P-CIC6H4, 0-, m-, or p-MeOC(iH4, P-CF3C6H4, a-thienyl, a-naphthyl (657). 

TAPA has been prepared only as described in this procedure. o -(Isopropylideneaminooxy)propionic acid has been prepared and resolved by the present procedure and has been prepared directly from a-bromopropionic acid and resolved as the (—)-ephedrine salt by crystallization from hydrocarbon mixtures. ... 

A number of syntheses of (V-hydroxy-a-amino acids and derivatives thereof have been reported. a-Bromocarboxylic acids or their r-butyl esters can be treated with hydroxylamine or 0-alkylated hydroxylamines to give the corresponding hydroxylamine derivatives. yV-Benzyloxy-t-alanine has been obtained by reaction of (/ )-a-bromopropionic acid with O-benzylhydroxylamine. But due to bromide exchange the optical yield was low. Anchimeric assistance of a suitable attached thio group can bring... 

Shortly after the product launch, the original process was modified (Scheme 2). Zinc chloride was removed from the coupling reaction, and ethyl bromopropionate was replaced with bromopropionic acid magnesium chloride salt. Most importantly, the resolution agent cinchonidine was replaced with A -alkylglucam-ine, which can be readily obtained from the reductive amination of o-glucose. 

The temperature at which the reaction is carried out, and the proportion of bromine used, determine the number of bromine atoms introduced. Thus, propionic acid when treated at 100° with phosphorus and bromine gives a-bromopropionic acid, CHsCHBr.COOH and at 220° with an excess of bromine, a, o-dibromopropionic acid, CH3CBr2.COOH. 

The optical isomers of alanine have been prepared by amination of n- and v-a-bromopropionic acids. The latter have been prepared by the action of PC1, and acetyl chlo-nde on n-serine methyl ester hydrochloride (904), by tiie action of nitroqrl bromide on n-alanine (289), and by the resolution of nir -bromopropionic add (147,6S4-656,507, 845). The preparation of n-alanine by the action of yeast on nn-alanine has been described by Ehrlich (234). L-Alanine has been prepared by the actimi of takadiastase (408, 584) and n-amino add orddase (79, 229) obtained from sheep or hog kidneys. The last author (Behrmn) isolated 22 g. of nearly pure ir-alanine from the reaction products of 72 g. of on-alanine. The velodty of the oxidation of i>-alanine by o-amino add oxidase has been determined by Stadie and Zapp (7S2). 

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