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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.

Etodolac methyl ester is a key intermediate in the synthesis of Etodolac, a non-steroidal anti-inflammatory drug. It can be obtained by oxa-Pictet-Spengler reaction, starting from 7- ethyltriptophol and using inorganic mineral acids as catalysts.[1] In order to get kinetic profiles of reactions catalyzed with different molar ratios of sulfuric and hydrochloric acid, a high performance liquid chromatography method with UV detection was developed for monitoring conversion of 7-ethyltryptophol to methyl ester of Etodolac. For that purpose different stationary phases (C18, Phenyl and NH2 column) were investigated for separation of 7-ethyltryptophol and Etodolac methyl ester. Elution was performed with three different solvent mixtures in isocratic and/or gradient mode. The best chromatographic separation was achieved isocratically using Waters Symmetry Shield RP 18 column with 55% acetonitrile and 45% water.