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Synthesis of (±)‐trans‐6‐[4,4‐bis(4‐fluorophenyl)‐3‐ (1‐methyl‐1H‐tetrazol‐5‐YL)‐1(E),3‐[2‐ 14 C] butadienyl]‐4‐hydroxy‐3,4,5,6‐tetrahydro‐2H‐pyran‐2‐one
Author(s) -
Luke G. M.,
Swigor J. E.
Publication year - 1991
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.2580290209
Subject(s) - chemistry , phosphonate , alkylation , yield (engineering) , hydrolysis , methyl iodide , acetic acid , lactone , alcohol , carbanion , medicinal chemistry , stereochemistry , organic chemistry , catalysis , materials science , metallurgy
A convergent synthesis of the title compound (BMY‐22089) is described. [ 14 C]Methyl iodide was used to alkylate 1,5‐dimethyltetrazole which was added to 4,4′‐difluorobenzophenone to give the tertiary alcohol 4 . Dehydration gave, the olefin 5 which was brominated and converted to the phosphonate 7 with trimethylphosphite. Coupling of the carbanion of 7 with cis‐2,2‐dimethyl‐6‐formyl‐1,3‐dioxane‐4‐acetic acid tert‐butyl ester ( 8 ) produced the diene 9 . Sequential hydrolysis steps using acid and base gave the dihydroxy acid 11 which was converted to the lactone 12 with the use of dicyclohexylcarbodiimide. The overall yield was 20%.