Ethyl bromo acetate

This preparation illustrates the Reformatsky reaction, which consists in the interaction of a carbonyl compound, an a-halogen ester (e.g., ethyl bromo-acetate) and zinc In the presence of ether or benzene, followed by hydrolysis. 

Hydrazinopyridazines such as hydralazine have a venerable history as anti hypertensive agents. It is of note that this biological activity is maintained in the face of major modifications in the heterocyclic nucleus. The key intermediate keto ester in principle can be obtained by alkylation of the anion of pi peri done 44 with ethyl bromo-acetate. The cyclic acylhydrazone formed on reaction with hydrazine (46) is then oxidized to give the aromatized compound 47. The hydroxyl group is then transformed to chloro by treatment with phosphorus oxychloride (48). Displacement of halogen with hydrazine leads to the formation of endralazine (49). ... 

In parallel fashion, compound 267, made from 2,3 5,6-di-<9-isopropyl-idene-D-mannono-1,4-lactone by Reformatsky addition using ethyl bromo-acetate and zinc-silver graphite, undergoes ready elimination when converted to the methanesulfonic ester to give a separable mixture of the E- and Z-alkenes (268).251 Quite a different approach involves treatment of the 1-C-nitromannofuranosyl chloride, derived from the oxime of 2,3 5,6-di-O-isopropylidene-D-mannose, with the anion of diethyl malonate to give the disubstituted alkene 269.252... 

RX. n-butyl bromide n-dodecanyl iodide cyclohexyl iodide ethyl bromo acetate methyl 2,3-di-O-acetyl-4-O-benzoyl-6-bromo-6-deoxy-ot-D-glucopyranoside methyl 2,3,4-tri-0-acetyl-6-deoxy-6-iodo-0 -D glucopyranoside l,2 3,4-di-0-isopropylidene-6-deoxy-6-iodo-a-D-galactopyranose methyl 2(R)-[(tert-butoxycarbonyl)amino]-3-iodo-propionate cyclic bis(trifluoromethyl)oxazolidinone bromide. 

Alkylation of (4) with ethyl bromo acetate was effected under phase-transfer conditions with powdered potassium hydroxide and tetrabutyl ammonium bromide in tetrahydrofuran to yield compound (5), and the azide function in (5) was then reduced by catalytic hydrogenation (over Pd/C) to give (6). The aminoester (6) was resolved into its enantiomers via... 

Metallic zinc (8 g., 0.12 gram atom) is added to a solution of 18.2 g. (0.10 mole) of benzophenone and 20 g. (0.12 mole) of ethyl bromo-acetate in 90 ml. of sodium-dried benzene. The mixture is warmed cautiously on a water bath under a reflux condenser until initiation of reaction, at which point the heating bath is removed and the flask is cooled as needed to keep the reaction mder control but not enough to stop the reaction. The mixture is then heated to reflux for 45 minutes. The cooled mixture is treated with excess dilute sulfuric acid, the benzene layer is separated and washed with dilute acid, and the benzene is allowed to evaporate. The residual ester is... 

Reaction with organoboranes.1 Brown has extended the reaction of ethyl bromo-acetate with trialkylboranes to ethyl dibromoacetate. If one equivalent of potassium r-butoxide is used, an a-halocarboxylic acid is obtained dialkylation is achieved by use of two equivalents of the base. Since the first reaction occurs readily at 0°, whereas the second requires a higher temperature (50°), two different alkyl groups... 

Homologation Acrolein. Carbon monoxide. Cuprous bromide-Diazomethane. Ethyl bromo acetate. Ethyl diazoacetate. Methyl vinyl ketone. Phenylthiomethyllithium. Trimethyl phosphite. 

C4H7BrOj Ethyl bromo-acetate 158.2 C H Br Bromobenzene 156.1 CioHu... 

For example, after acetophenone (72 g) has been allowed to react with ethyl bromo-acetate (100 g), and zinc turnings (41 g) in benzene (250 ml), the solvent is distilled off and the residue is treated with phosphorus oxychloride (20 drops). Distillation then gives ethyl -methylcinnamate (80 g) as the fraction boiling at 155-165°/28 mm.221... 

This dithiocarbonate is prepared in 92% yield by the reaction of ethyl bromo-acetate with carbon disulfide, ethanol, and KOH. 

Pyrrolidine added to a soln. of 127 g. 5-methoxy-2-tetralone in benzene, refluxed 7 hrs. in a flask provided with a water separator, the benzene removed by distillation, the residue dissolved in dioxane, heated to reflux, ethyl bromo-acetate in dioxane added, and refluxing continued 22 hrs. under Ng 178 g. keto ester. R. W. Guthrie et al., Coll. 31, 602 (1966). 

Ethyl 3-hydroxyisonicotinate, all lated by ethyl bromo-acetate and ethyl o-bromo-propionate, 767... 

Organoboranes can also be used to construct carbon-carbon bonds by several other types of reactions involving migration of a boron substituent to carbon. One such reaction involves a-halocarbonyl compounds.For example, ethyl bromo-acetate reacts with trialkylboranes in the presence of base to give alkylated acetic acid derivatives in excellent yield. The reaction is most efficiently carried out with a 9-BBN derivative. 

Heating 1-phenyl-1-benzoylcyclopropane with excess ethyl bromo-acetate and 20-mesh zinc at reflux for 17 h gave a 47% yield of the Reformatsky product along with 55% recovered ketone [85]. What could be done to improve this reaction ... 

---