Microwave‐Assisted Elimination Reaction of trans‐4‐(4‐Fluorophenyl)‐3‐chloromethyl‐1‐methylpiperidine on Alumina

Abstract

trans‐4‐(4‐Fluorophenyl)‐3‐chloromethyl‐1‐methylpiperidine 3b was subjected to elimination reaction on alumina or KF‐alumina under solvent‐free conditions and microwave irradiation. Compared with the “classical” method of heating in the presence of an organic base, the microwave‐assisted methodology provided higher yields of 4‐(4‐fluorophenyl)‐3‐methylene‐1‐methylpiperidine 7b (65.5–71%) in considerably shorter reaction times (20–40 min). Furthermore, the exocyclic double bond in 7b underwent rearrangement to the endocyclic double bond to furnish compound 8. The effect of alumina and irradiation time on reaction conversion and the extent of isomerization was examined.

Keywords:

• Elimination reaction
• Alumina
• Microwave irradiation
• trans‐4‐(4‐Fluorophenyl)‐3‐chloromethyl‐1‐methylpiperidine
• Dehydrohalogenation
• Paroxetine
• Solid support

Acknowledgments

The authors thank Mr. R. Kareš for his technical assistance and Professor A. Loupy for fruitful discussions. Financial support from the Ministry of Education of the Czech Republic (Grant No. J07/98: 143100011 and COST OC D 10.20) is gratefully acknowledged.