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Updated: Aug 7, 2026

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Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
A simplified and efficient synthesis of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF)
E C Taylor1, R Chaudhari, K Lee
1Department of Chemistry, Princeton University, NJ 08544, USA.
Investigational New Drugs
|January 1, 1996
Abstract:
A new and extremely efficient synthesis of DDATHF from 4-vinylbenzoic acid and bromomalondialdehyde as precursors has been developed which proceeds in 48% overall yield.
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As shown below, the mechanism involves a nucleophilic attack by water at the carbonyl carbon to form a tetrahedral intermediate. This is followed by the reformation of the carbon–oxygen π bond along with the departure of a halide ion. A final proton transfer step yields carboxylic acid...
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