Hi Jigar,

I had a quick look at this route, and since it is a multi-step synthesis, it could be one (or more) of the steps which is the source of your problem. Have you narrowed down the source of the low yield to one of the steps in particular, or are they all performing poorly?

My first thought is that the hydrogenation of the pyridine to the piperidine is most likely to be the problem, since hydrogenations requiring high pressure can be difficult to drive to completion. Are you following this by measuring hydrogen uptake and waiting until 3 equiv are absorbed?

Please provide some more details of where you think you're losing your yield, and I'm sure plenty of people will be able to make some helpful suggestions!

thank you sir for suggestion.

and extremly sorry for the delayed reply for my side.

I had also taken ehtyl isonipecoate as a starting material..

but I am facing problem in the cyclization step for the same i am using the method described in Org syn coll vol..

I think aqueous potassium carbonate can hydrolyse ester functionality and acid is going in aqueous layer, i think it will be better if you change it to methonolic ammonia to make free base.

use 5% pt/c for hydrogenation of pyridine to piperdine, this you can do at still lower pressure. even Rh/c will still give good results

dr uday joshi---pune