- A NEW METHOD OF MANUFACTURING 2-(6-(4-CHLOROPHENYL)-2,2-DIMETHYL-7-PHENYL-2,3-DIHYDRO-LH-PYRROLIZINE-5-YL)ACETIC ACID (LICOFELONE)
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A method of manufacturing 2-(6-(4-chlorophenyl)-2,2-dirnethyl-7-phenyl-2,3-dihydro-lH- pyrrolizine-5-yl)acetic acid of formula I, wherein 6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl- 2,3-dihydro-lH-pyrrolizine of formula II is alkylated with a iodo derivative of formula VII, wherein A is either the cyano group CN or an ester group COOR, wherein R is an (un)branched C1-C6 alkyl group, with the use of the Fenton reagent in the presence of a sulfoxide of formula R1-SO-R2, wherein R1 is an (un)branched C1-C12 alkyl group, R2 is either an (un)branched C1-C12 alkyl group, an aryl group or a substituted aryl group, or wherein R1, R2 are independently (CΗ2)mX(CΗ2)n, wherein X = CH2, O, S, NR3, m = 1-3, n = 1-3 and R3 is either an (un)branched C1-C12 alkyl group, an aryl group or a substituted aryl group, the reaction being carried out in the environment of the sulfoxide used or in its mixture with suitable solvents at a temperature of O 0C to 80 °C, preferably at temperatures in the range of 10 to 40 °C, and the resulting ester of formula IV or nitrile of formula VIII is hydrolyzed to the desired product of formula I either directly or in the case of the nitrile via the amide of formula (IX).
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Page/Page column 7-8; 12-13
(2009/06/27)
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- A synthesis of licofelone using Fenton's reagent
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An efficient synthesis of licofelone, an anti-inflammatory drug currently undergoing phase-III clinical studies, based on Fenton-type radical alkylation of 2,3-dihydro-1H-pyrrolizine 3 with iodoacetonitrile or iodoacetates is reported. The iodoacetates can be replaced by NaI and by the corresponding bromoacetate.
- Rádl, Stanislav,?erny, Josef,Klecán, Ond?ej,Stach, Jan,Pla?ek, Luká?,Mandelová, Zuzana
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p. 5316 - 5318
(2008/12/22)
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