engleski

KINETIC STUDY OF MINERAL ACID-CATALYZED CONVERSION OF 7-ETHYLTRIPTOPHOL TO METHYL ESTER OF ETODOLAC

Etodolac, 1, 8-diethyl-1, 3, 4, 9-tetrahydropyrano- [3, 4-b]indole-1-acetic acid is a non-steroidal antiinflamatory antirheumatic drug. A key intermediate in the synthesis of Etodolac is its methyl ester which can be obtained by oxa- Pictet-Spengler reaction, starting from 7- ethyltriptophol. Pyrano[3, 4-b]indole ring is closed in the reaction of 7-ethyltriptophol and β-ketoester, methyl 3-oxo-pentanoate. For the preparation of oxacycle (pyranic ring) different Brönsted and Lewis acids can be employed.[1] Typically, aqueous hydrochloric or sulfuric acid, as well as boron trifuoride etherate, gasous hydrochloride, p- toluensulfonic acid, zink chloride, aluminium chloride and tin(IV) chloride in organic solvents are used to promote the reaction. Catalyst such as boron trifuoride etherate is expensive and is stable only in a perfectly anhydrous environment, which is difficult to manage, especially in productions on a larger scale. Therefore, the processes in which inorganic mineral acids can be used are preferred.[2] We report the kinetic study of conversion of 7-ethyltriptophol to methyl ester of Etodolac in methanol in the presence of concentrated hydrochloric and sulfuric acids. In order to optimize the synthetic procedure, kinetic profiles of reactions promoted with different molar ratios of acids (with respect to the β-ketoester) were determined using HPLC as a method of choice.

Oxa Pictet Spengler reaction; mineral acid promoter; kinetic study

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