Methods of making 2,6-diaryl piperidine derivatives
View Patent ↗Methods for preparing 2,6-diaryl piperidine derivatives are described. More particularly, 2,6-diaryl piperidines having formula 1-4 are prepared by cyclocondensation of an aryl or heteroaryl aldehyde with 1,3-acetonedicarboxylic acid.
1. A method of making a compound of formula (3)
comprising contacting a compound of formula (4)
with a compound of the formula
X-L-Y
wherein X is a leaving group;
L is —(CH 2 ) 4 —;and
Y is phthalimide.
2. The method of claim 1 , wherein X is halo.
3. The method of claim 1 , wherein X is bromo.
4. The method of claim 1 further comprising reacting the compound of formula (3) with hydrazine hydrate to obtain a compound of formula (5)
5. The method of claim 1 , wherein the compound of formula (4) is prepared by reacting a compound of formula (6)
with hydrazine monohydrate in the presence of potassium hydroxide.
6. A method to prepare a compound of the formula (5)
comprising the steps of:
reacting a compound of the formula (6)
with hydrazine monohydrate in the presence of potassium hydroxide, to obtain a compound of formula (4)
followed by
reacting the compound of formula (4) with 2-(4-bromo-butyl)-isoindole-1,3-dione, to obtain a compound of formula (7); and
deprotecting the compound of formula (7) with hydrazine hydrate.