Chlorophenoxyisobutyrate

The ethyl p-chlorophenoxyisobutyrate may be obtained by heating a mixture of 206 parts of dry p-chlorophenoxyisobutyric acid, 1,000 parts of ethanol and 40 parts of concentrated sulfuric acid under reflux during 5 hours. The aicohol is then distilled off and the residue is diluted with water and extracted with chioroform. The chloroform extract is washed with sodium hydrogen carbonate solution, dried over sodium sulfate and the chloroform removed by distillation. The residue is distilled under reduced pressure and there is obtained ethyl p-chlorophenoxyisobutyrate, BP 148° to 150°C/20 mm. 

The p-chlorophenoxyisobutyric acid used as starting material may be obtained as follows. 

When addition is complete the mixture is heated under reflux during 5 hours and then the acetone is removed by distillation. The residue is dissolved in water, acidified with hydrochloric acid and the mixture extracted with chloroform. The chloroform extract is stirred with sodium hydrogen carbonate solution and the aqueous layer is separated. The alkaline extract is acidified with hydrochloric acid and filtered. The solid product is drained free from oil on a filter pump, then washed with petroleum ether (BP 40° to 60°C), and dried at 50°C. The solid residue, MP 114° to 116°C, may be crystallized from methanol (with the addition of charcoal) to give p-chlorophenoxyisobutyric acid, MP 118° to 119°C. 

Chemical Name 3-(Dimethylaminocarbonyl)-propyI-4 -chlorophenoxyisobutyrate Common Name —... 

Chemical Name 2-(4-Chlorophenoxy)-2-methylpropanoic acid ethyl ester Common Name Ethyl p-chlorophenoxyisobutyrate Structural Formula ... 

The p-chlorophenoxyisobutyric acid used as starting material may be obtained as follows. A mixture of 200 parts of p-chlorophenol, 1,000 parts of acetone and 360 parts of sodium hydroxide pellets is heated under reflux and 240 parts of chloroform are gradually added at such a rate that the mixture continues to reflux without further application of heat. 

Synonyms. Ethyl Chlorophenoxyisobutyrate Ethyl Clofibrate. Proprietary Names. Amotril Atheropront Atromidin Atromid-S Azionyl Claripex Clofibral Clofirem Lipavlon Liprin(al) Normolipol Novofibrate Regelan Skleromexe. 

Clofibrate is rapidly and completely absorbed after oral administration. It is hydrolyzed to clofibric acid during absorption and in its passage through the liver. The acid binds strongly to plasma proteins. Sixty percent of it is excreted as glucuronide conjugate in the urine. Some is secreted into the bile and reabsorbed. The plasma elimination half-life is 25 h. Clofibrate appears in plasma as p-chlorophenoxyisobutyric acid. An acyl-linked metabolite of clofibrate has been identified in human urine. 

Atromld S (CPIB, ethyl chlorophenoxyisobutyrate) has now been released for sale in the U.S.A. Reports of its effectiveness in lowering serum triglycerides and senrni cholesterol continue to appear. It has shown effectiveness in the diabetic with concomitant disappearance of retinal... 

Clofibrate Chlorophenoxyisobutyric acid Primarily responsible for hypolipidemic effect and direct muscle toxicity... 

Falls in serum alkaline phosphatase have also been reported with nafenopin (D17) and chlorophenoxyisobutyrate (HIO). In contrast, colestipol therapy given over many months results in a significant rise in serum alkaline phosphatase (M15). It has been suggested that some of the effects of antilipidemic agents may be related to their action on vitamin D absorption (G25). 

Reddy, J. K., and Qureshi, S. A. (1979). Tumorigenicity of the hypolipidaemic peroxisome proliferator ethyl-alpha-p-chlorophenoxyisobutyrate (clofibrate) in rats. Br J Cancer 40, 476-482. 

Clofibrate, the prototype of the fibric-acid derivatives, is the ethyl ester of p-chlorophenoxyisobutyrate. Gemfibrozil is a nonhalogenated phenoxypentanoic acid and thus is distinct from the halo-generated number of fibric-acid analogs (e.g., fenofibrate, bezafibrate, and ciprofibrate have been developed and are used). 

Thorp JM, Waring WS. Modification and distribution of lipids by ethyl chlorophenoxyisobutyrate. Nature 1962 194 948-949. 

Malhotra, S.C., and M.M. Ahuja. 1971. Comparative hypolipidaemic effectiveness of gum guggulu (Commiphora mukul) fraction A, ethyl-p-chlorophenoxyisobutyrate and Ciba-13437-Su. Indian J. Med. Res. 59(10) 1621-1632. 

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