Bromovalerate

METHYL B-BROMOVALERATE (Valeric acid, 8-bromo-, methyl ester) 

Submitted by C. F. H. Allen and C. V. Wilson. Checked by Cliff S. Hamilton and Noboru Tosava. 

To a solution of 33 g. (O.S mole) of potassium hydroxide (Note 1) in 1.5 1. of distilled water in a 5-1. flask or other appropriate container fitted with a mechanical stirrer is added 80 g. (0.5 mole) of methyl hydrogen adipate (Note 2). With continuous stirring a solution of 85 g. (0.5 mole) of silver nitrate in 1 1. of distilled water is added rapidly (about IS minutes). The precipitated methyl silver adipate is collected on a Buchner funnel, washed with methanol, and dried in an oven at 50-60°. For the next step the dried silver salt is finely powdered and sieved through a 40-mesh screen. The combined yield from two such runs is, 213 g. (80%). 

The 213 g. (0.8 mole) of finely powdered silver salt is placed in a 1-1. three-necked flask (Note 3) two necks of the flask are stoppered, and the third is connected to a water pump through a U-tube or flask containing Drierite. The flask is then placed in an oil bath and evacuated to a pressure of about IS mm. The temperature of the oil bath is maintained at 100-110 for 36 hours (Notes 4 and S). 

Reagent grade potassium hydroxide containing 85% potassium hydroxide is used. 

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This method with some slight modihcations is applied in the synthesis of to-bromo esters from Cs to Cn. Methyl 5-bromovalerate has been prepared by treating the silver salt of methyl hydrogen adipate with bromine. The ethyl ester has been prepared from the acid by esterification or through the acid chloride. ... 

Sodium hydride, 50% dispersion in mineral oil Alpha Inorganics Ethyl 5-bromovalerate A... 

Ethyl bromopyruvate, e91 Ethyl bromovalerate, e92 Ethyl butanoate, e99 2-Ethylbutyl alcohol, e95 Ethyl butyl ether, b554... 

Ethyl benzyl ether, b95 Ethyl bromovalerate, e80 Ethyl caproate, el 42 ... 

Carboxylic acids, acyl chlorides, and sulfonyl chlorides used for deri-vatization of 4-aminophenylalanine and >-4-am i n op h e ny I a I a n i n e are as follows 5-hydantoinacetic acid, / ran, v - 4 - co t i n i n ec a r b o xy I i c acid, isonicotinic acid, 3-pyridinepropionic acid, 4-hydroxyphenylacetic acid, 2-butynoic acid, 2-pyrazinecarboxylic acid, cyclopropanecarboxylic acid, 3-hydroxy-2-qui-noxaline carboxylic acid, 5-bromovaleric acid, propargyl chloroformate, 3,4-dimethoxybenzoyl chloride, 2-thiophenesulfonyl chloride, 3-thiophene-carboxylic acid, 2-thiophenecarboxylic acid, 2-methylbutyric acid, 2-thio-pheneacetyl chloride, benzoic acid, furylacrylic acid, 4-nitrophenyl acetic acid, 2,5-dimethoxyphenylacetic acid, p-toluenesulfonyl chloride, 4-(di-methylamino)phenylacetic acid, 3-indolepropionic acid, phenoxyacetic acid, 3-(dimethylamino)benzoic acid, cyclohexanecarboxylic acid, naphtha-lenesulfonyl chloride, 4-bromophenylacetic acid, 4-bromobenzoic acid, 2-phenoxybutyric acid, 3,4-dichlorophenylacetic acid, (l-naphthoxy)acetic acid. 

Methyl /3-brohopropionatk, 20, 64 Methyl 5-bromovalerate, 26, 52 Methyl- -butylamine, 25,19... 

The Step 3 product (0.89 mmol) and methyl 5-bromovalerate (0.98 mmol) dissolved in 3.3 ml acetonitrile were treated with K2C03 (1.95 mmol), then refluxed 48 hours, and concentrated. The residue was dissolved in EtOAc, then washed with water, dried using Na2S04, and concentrated. The residue was purified by chromatography using cyclohexane/EtOAc, 5 1, and the product isolated in 78% yield as a colorless oil. 

An Algox Pharmaceutical group reported a preparation of MNA capitalizing on a C5 + C5 strategy, and based on the alkylation of bromovaleric add (S2) with the lithium anion of 3-methyl-l-butyne (S3), followed by stereoselective reduction of 8-methyl-6-noninoic acid (S4) to ( )-MNA by dissolving-metal reduction. 

A reactor was charged with polyethylene glycol (0.5 mol M 10,000), and treated with 50 ml of toluene, and azeotropically dried by refluxing for 2 hours. The resulting mixture was dissolved in 30 ml of THF and treated dropwise with sodium hydride (5 mmol) dissolved in 20 ml of THF and refluxed overnight. This mixture was then treated with ethyl-5-bromovalerate (5 mmol) and refluxed overnight and concentrated. The residue was precipitated by the addition of 2-propanol/diethyl ether, 1 1, and then fdtered to yield 4.5 g of isolated product. 

Ethyl 5-bromovalerate Pentanoic acid. 5-bromo-, ethyl ester (14660-52-7), 76, 255... 

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