Ethyl-a-bromopropionate

Ethyl a-bromopropionate. This preparation illustrates the facile bromination of an acid chloride (propionyl chloride) in the presence of red phosphorus, and the subsequent conversion of the bromoacid chloride into the ethyl ester by direct interaction with ethanol. 

Chapter III. 1 Heptene (111,10) alkyl iodides (KI H3PO4 method) (111,38) alkyl fluorides (KF-ethylene glycol method) (111,41) keten (nichrome wire method) (111,90) ion exchange resin catalyst method for esters (111,102) acetamide (urea method) (111,107) ethyl a bromopropionate (111,126) acetoacetatic ester condensation using sodium triphenylmethide (111,151). 

The reaction of ethyl a-bromoacetate with 17-keto steroids such as estrone methyl ether or dehydroepiandrosterone acetate " under standard Reformatsky conditions is stereospecific, producing the 17 -ol in up to 80% yields. Ethyl a-bromopropionate reacts similarly but the yields are somewhat lower. 

Ethyl a-(1-pyrrolidyl)-propionate has been prepared by the reaction of pyrrolidine with ethyl a-bromopropionate.2... 

Ethyl a-bromopropionate is available commercially (Sapon Laboratories, % 1.4452) and is employed without purification. Bromo esters are severe lachrymators, and operations that involve transferring these compounds from one vessel to another should be conducted in a well-ventilated hood. 

Eastman grade ethyl a-bromopropionate was used as obtained from Eastman Organic Chemicals. 

Ethyl isocyanide, 46, 76, 77 Ethyl a-(isopropylideneaminooxy)pro-pionate, from acetone oxime and ethyl a-bromopropionate, 48,120 hydrolysis of, 48,121 Ethylmagnesium bromide, use with ferric chloride in cyclization of di-chloroacetone /J-Lolylmagncsium bromide adduct to l-f>-tolyicy-clopropanol, 47,108 Ethyl a-methyl-/3-phenylcinnamate, 48, 79... 

Selective N-alkylation of potassium phthalimide by ethyl a-bromopropionate"... 

L-Perhydro-l,4-thiazine-3-carboxylic acid 1-oxide is a natural AA found in some red and brown algae. It was synthesized from L-cystine in several steps. The heterocyclic ring was prepared by cyclization of 5-(2-chloro- or bromoethyl)-L-Cys in the presence of triethylamine. Perhydro-l,4-thiazine-3-carboxylic acid was then oxidized with H2O2/ACOH to give the sulfoxide (64JOC2203). Cystine also reacted with ethyl a-bromopropionate in liquid ammonia to give 5-oxoperhydro-l,4-thiazine-3-carboxylic acid [76JCS(P2)203],... 

The Reformatsky reactions of ethyl a-bromopropionate and related esters with N-substituted 6-bromo-2-oxochromene-3-carboxamides in a mixed diethyl ether-benzene-HMPA-THF solvent system give substituted 9-bromo-2,3,4,4a,5,10b-hexahydro-l//-chromeno[3,4-f]pyridine-2,4,5-triones (HMPA = hexamethylphosphoramide Scheme 45) <2004RJ0892>. Without the THF present in the mixed-solvent system, the reaction stops at the intermediate Wbenzyl-6-bromo-4-(l-alkoxycarbonylalkyl)-2-oxochroman-3-carboxamide stage. 

Ethyl a-bromopropionate [535-11-5] M 181.0, b 69-70 /25mm, d 1.39, n 1.447. Washed with saturated aqueous Na2CO3 (three times), 50% aq CaCl2 (three times) and saturated aqueous NaCl (twice). Dried with MgSOa, CaCl2 or CaCO3, and distd. LACHRYMATORY. 

Ethyl N-benzylcarbamate, 35, 91 Ethyl 3-benzyl 2 cyano 3 methyl-pentanoate, 35, 7 Ethyl bromide, 34, 58, 36, 87 Ethyl a-bromobutyrate, 37, 44 Ethyl a bromopropionate, 35, 17, 37, 38... 

The method was originally proposed by Clemo and Metcalfe47 for the preparation of 3,5-dimethylpyrrolizidine. Condensation of ethyl (5-methyl-2-pyrrolidyl)acetate with ethyl a-bromopropionate resulted in the corresponding dicarboxylate (77), which was converted by cyclization and subsequent hydrolysis and decarboxylation into 3,5-... 

In another example of oxidation without fission, the major product obtained from the reaction of methyl 2-pyridylacetate with ethyl a-bromopropionate was not the expected indolizine (63) but its oxidation product (64). This was shown by a repetition of the reaction under nitrogen leading to (63), which subsequently could be oxidized to (64) by potassium ferricyanide (70JCS(C)1434). An oxidative dimerization at the 3-position of 1,2-dimethylin-dolizine was achieved with potassium ferricyanide (71TL1273) or palladium on charcoal in boiling xylene (81BCJ2833). 

This method is suitable for the preparation of mono- and di-a-substituted /3-ketoesters. Bromoacetates fail in this reaction. Yields with ethyl a-bromopropionate are considerably lower (30-36% with capronitrile) however, ethyl esters are useful for higher-molecular-weight compounds whose sec-alkyl esters are cracked by distillation. With 3-pentyl a-bromopropionate, the yields are slightly higher (53-60% with capronitrile). Both aromatic and aliphatic nitriles are suitable benzonitrile gives yields comparable to those obtained with capronitrile. Alkyl substitution in the a- and /8-positions (cf. Note 4) of aliphatic nitriles lowers the yield to 29% and 38%), respectively 7-substitution has no effect. 

The products were isolated as esters by reaction of the acylcobalt carbonyls with an alcohol and iodine. In the case of the alkyl halides, carbon monoxide was normally absorbed, but under nitrogen, acylcobalt tricarbonyls must be formed. The reaction with alkyl halides was slow and some isomerization was noted using M-propyl iodide (formation of n-butyrates and isobutyrates). Absence of carbon monoxide promoted the isomerization. Isopropyl iodide gave no reaction. When ethyl a-bromopropionate was used, no isomerization was found at — 25 °C under carbon monoxide, but the isomerized product, diethyl succinate, was the major product at 25° C under carbon monoxide or nitrogen. Under the conditions of the experiments no isomerization of the alkyl halide itself was found. 

The site at which alkylation occurs depends on the alkylation reagent, the reaction conditions and the nature of the substituents on the azoloazine ring system. Thus, whereas alkylation of compound (114) by alkyl iodides in THF in the presence of sodium hydride gives the products (115), alkylation by ethyl a-bromoacetate or ethyl a-bromopropionate gives the products (116) (Scheme... 

In 1980, Kagan reported the first example of a Sml2-mediated Reformatsky reaction.98 Kagan s study involved the coupling of ethyl a-bromopropionate with cyclohexanone (Scheme 5.88). 

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