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Synthesis of nornicotine‐2,4,5,6‐d 4 and its N′‐nitroso derivative
Author(s) -
Munson James W.,
Hodgkins Thomas G.
Publication year - 1977
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2580130402
Subject(s) - chemistry , thionyl chloride , sodium borohydride , nornicotine , pyridine , trimethylsilyl chloride , derivative (finance) , morpholine , medicinal chemistry , organic chemistry , butyllithium , chloride , alkaloid , financial economics , economics , catalysis
Nornicotine‐2,4,5,6‐d 4 and its N′‐nitroso derivative were synthesized from pyridine‐d 5 . Initially, pyridine‐d 5 was brominated in fuming D 2 SO 4 to give 3‐bromopyridine‐d 4 . Treatment of this material with n‐butyllithium and dry ice followed by acidification gave nicotinic acid‐2,4,5,6‐d 4 . Conversion of this substance to the acid chloride hydrochloride (via thionyl chloride) followed by treatment with absolute ethanol gave ethyl nicotinate‐2,4,5,6‐d 4 . The ester was condensed with N‐trimethylsilyl‐2‐pyrrolidinone in the presence of n‐butyllithium and diisopropylamine to give, after hydrolysis and decarboxylation, myosmine‐2,4,5,6‐d 4 . Reduction of this material with sodium borohydride gave nornicotine‐2,4,5,6‐d 4 . Conversion to the N′nitroso derivative was achieved by treatment with nitrous acid.