Preparation of 4-(4-fluoropheny)-1-methyl-3-methylenepiperidine by Microwave-assisted Elimination Reaction
| Authors | |
|---|---|
| Year of publication | 2003 |
| Type | Article in Proceedings |
| Conference | Speaker's Presentation & materials |
| MU Faculty or unit | |
| Citation | |
| Field | Organic chemistry |
| Keywords | Microwave-assisted; Elimination |
| Description | Paroxetine 1 is an antidepressive drug belonging to a family of selective serotonine-reuptake inhibitors used in the treatment of depression and Parkinsons disease.1,2 The drug is marketed as a hydrochloride in an enantiopure form with the (3S,4R)-configuration under the name of Paxil and Seroxat. trans-4-(4-Fuorophenyl)-3-hydroxymethyl-1-methylpiperidine 2 (Z=OH) is an important racemic intermediate of a paroxetine multi-step synthesis which is subjected to the optical resolution to provide a desirable (3S,4R)-enantiomer and a chiral waste highly enriched in the opposite enantiomer.3 In our communication we report on the initial steps of a suggested route to transform the waste enantiomer (3R,4S)-2 into its antipode. Elimination reaction performed with compounds 2-5 was attempted using microwave irradiation and a solid support4 to yield elimination product 6 that in some cases underwent isomerization to 7 (Scheme). The reaction yield depended on the substrate, the type of solid support, support/substrate ratio and irradiation time. The best results (65.5-71% yield) were obtained with a chloroderivative 3 when alumina impregnated with KF was used as a solid support and the irradiation time ranged from 20 to 40 min. |
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