Ethyl-2-bromopropionate

To the crude mixture of ammonium bromide and /3-bromo-propionic acid, prepared as described on p. 25, from 317 g. of ethylene cyanohydrin, are added 1200 cc. of carbon tetrachloride and 200 cc. of the same solvent which has been shaken with the aqueous distillates the ammonium bromide is filtered off and washed with 200 cc. of carbon tetrachloride. The watery layer, amounting to about 350 cc., is separated and shaken with 100 cc. of carbon tetrachloride. To the united carbon tetrachloride solutions are added 450 cc. of 95 per cent ethyl alcohol and 10 g. of sulfosalicylic acid or phenolsulfonic acid to act as a catalyst (Note 1). 

The esterification may be carried out without the addition of a sulfonic acid, as traces of hydrobromic acid generally remain in the crude material but since the time of operation must be kept as short as possible this omission is not recommended. It has been found that if the water be not removed and the mixture boiled under a reflux condenser for two hours before the distillate is passed through the automatic separator, the yield falls to 70-7 5 per cent of the theoretical amount. 

It is important to carry out the esterification as rapidly as possible in order to cut down to a minimum the formation of ethyl hydracrylate, which takes place by the action of water on the (3-bromopropionic acid or ester an efficient condenser is therefore necessary. For the same reason it is necessary to remove all residual water from the mixture before adding the alcohol. 

As in the preparation of the /3-bromopropionic acid, bemiene must not be substituted for the carbon tetrachloride, as it has been found impossible to make a satisfactory separation of this solvent from the ester. 

Ethyl (3-bromopropionate has always been prepared by the esterification of /3-bromopropionic acid.1 

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Ethyl a-bromoisobutyrate, 21, 53 Ethyl /3-bromopropionate, 20, 6S Ethyl caprylate, 20, 69 Ethyl carbonate, 23, 95, 97 Ethyl chlorocarbonate, 21, 81 2-Ethylchromone, 21, 42 Ethyl diacetylacetate, 21, 46 copper derivative, 21, 46 Ethyl a,a-DIMETHYL-/3-PHENYL-/3-hydroxypropionate, 21, S3 Ethylene chloride, 20, 28 22, 76 ETHYLENEDIAMINE, IV IV-DIBUTYL-, 23, 23... 

Ethyl /3-bromopropionate may be prepared in the same manner in about 90 per cent yield. The boiling point of the ethyl ester is 77-79° at 19 mm. 

Methyl acrylate did not react with ketene aminals 240 (R = Me, Cl) in dioxane at ambient temperature, but reactions took place on refluxing for 20-48 hours to yield hexahydro-6/f-pyrido[l,2-a]pyrimidin-6-ones 250 (R = Me, Cl) (86H2247 89SC1801). Hexahydro-6//-pyrido[ 1,2-a]-pyrimidin-6-one 250 (R = OMe) was also prepared in the reaction of ketene aminal 240 (R = OMe) and ethyl 3-bromopropionate in refluxing acetonitrile for 48 hours (89SC1801). Hexahydro-67/-pyrido[l, 2-cj] pyrimidin-6-ones 250 (R = H, Me, Cl, OMe) were prepared in better yields (79-91%) when the reaction mixture of ketene aminal 240 (R = H, Me, Cl, OMe) and an excess of methyl acrylate was irradiated in anhydrous methanol by a 450-W medium-pressure mercury lamp under nitrogen at ambient temperature for 3-5 hours (93SC1039). 

By the reaction of 2-aminopyridines with ethyl 3-bromopropionate in dimethylformamide at 130-150°C for 3-5 hours 2-oxo-3,4-dihydro-2//-pyrido[l,2-a]pyrimidines 256 were prepared (84MI17). 

Heptyl bromide was not hydrogenolyzed whatsoever, even in the presence of potassium acetate, while phenethyl bromide and 3-phenylpropyl bromide were hydo-genolyzed at considerable rates with addition of the base. Ethyl 3-bromopropionate, which resisted hydrogenolysis in neutral alcohol, as mentioned above, was hydrogenolyzed in the presence of the base, although at a slow rate. It is seen that the bomine located at the a-position is markedly activated by electron-withdrawing benzoyl and ethoxycarbonyl groups. 

When the mixture has reacted completely, set the round-bottomed flask in the ice-salt bath. Charge the addition funnel with ethyl 3-bromopropionate (128 mL, 181 g, 1 mol) and add it dropwise to the reaction mixture with rapid stirring. 

Prepd by electrolysis of a mixture of KN03, and potassium ethylsuccinate (Ref 2), or by treating AgNO 3 with ethyl 3-bromopropionate in acetonitrile (Ref 3)... 

Reactions of the Bislactim Ether Cuprate. The lithiated bislactim ether can be converted to an azaenolate cuprate by treatment with CuBr SMe2 (see Copper(I) Bromide)fi Conjugate addition of the cuprate to enones (eq 3) and dienones, or alkylation with base labile electrophiles like ethyl 3-bromopropionate, proceeds with high trans diastereoselectivity. Hydrolysis of the Michael... 

Kendall and McKenzie esterified crude B-bromopropionic acid (about 4 m.) by heating an ethanol-carbon tetrachloride solution containing 10 g. of sulfosalicylic acid under a water separator and obtained ethyl /3-bromopropionate in overall yield... 

Ethyl a-bromopropionate, 1286 Ethyl /3-bromopropionate, 1118 Ethyl bromopyruvate, 1217 Ethyl t-butyl malonate, 522, 523 Ethyl t-butyl oxalate, 210 Ethyl n-butyrate, 790 Ethyl carbamate, see Urethane S-Ethylcarbamoylcysteine, 383 Ethyl carbazate, see Ethoxycarbonylhydra-zine... 

Ethyl-3-diallylaminopropionate (XIV) was synthesized from ethyl 3-bromopropionate (20 g, 0.111 mol) to which diallyl-amine (29 g, 0.3 mol) was added slowly with stirring and heating at 100-105°C. After complete addition, heating was continued for another 15 min. The mixture then was cooled and water was added. The solution was basified with ammonia and the product extracted with chloroform and purified by distillation. 

The reaction of 3-thienyl-lithium, prepared by halogen-metal exchange of 3-bromothiophens, has been used for the synthesis of many geminal 3,3-dithienyl derivatives of pharmacological interest. Thus the reactions with ethyl 3-bromopropionate, ethyl cyclopropylcarboxylate, and (90) were used for the synthesis of (91), (92), and (93), respectively. The reaction of 3-thienyl-lithium with quinoxaline has been used for the preparation of... 

Ethyl 2-bromopropionate (ethyl 2-bromopropanoate) ethyl 3-bromopropionate (ethyl 3-bromopropanoate)... 

It has been published and patented that mPEG-propionic acid can be obtained by nucleophilic displacement reaction of mPEG-alkoxide with ethyl 3-bromopropionate or with halogenated 3-halopropionate substrates [78,79]. However, it was later indicated that the first method does not afford the required acid but the elimination product, due to the acid-base reaction of the hydrogen in the position a- to the carboxylic group [74]. 

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