I studied this literature extensively in the 1970s, including Abood's work, Biel's work, papers from Roche chemists, etc. I am now retracing my steps
from 30 years ago. Ditran the spamolytic was no accident; Ditran the experimental psychtomimetic for psychiatric use, was. And THAT is what the BZ
program came from.
As you can see in this paper 3-hydroxypyridine was indeed a feedstock but for reduction to the 3-hydroxypiperidine and alkylation to the desired
tertiary aminoalcohol. Making 3-quinuclidinol from that would not be trivial. The accepted process is to start with gamma-picoline, oxidize that to
the isonicotinic acid, wsterify that, N-alkylate it, reduce to the isonipeconic acid ester, and do a Dieckmann using potassium metal. That gets you
3-quinuclidone. Reduce that with LAH and what have you got?
[Edited on 14-7-2008 by Sauron] |