• 10.1021/jm00393a004
  • Journal of Medicinal Chemistry
  • Volume 30
  • October 1987
  • pp 1711-1715

Procedure Adapted for Better Synthesis


Wanting to avoid a chromatographic separation of the Me esters as well as the greater expense of dimethyl itaconate, the reaction of alpha methyl benzylamine and itaconic acid was performed in xylene.  The reaction was performed by adding the amine at 110 to a xylene suspension of itaconic acid.  Due to the acid base reaction, the mixture self-warmed to reflux causing homogeneity.  The reaction was complete in 3 hours rather than 24 hours as listed in the literature.  The reaction was cooled to 70 and MeOH was added followed by slow cooling.  This resulted in selective precipitation of a 94:6 mixture of diastereomers without seeding.  The acid could be further purified by recrystallization from 9:1 MeCN/water at 70 with seeding.  The filtrate was a 70:30 mixture of diastereomers from which the desired diastereomer could be isolated by concentration to remove MeCN.  This adapted procedure resulted in the easy isolation of diastereomerically pure carboxylic acid from inexpensive starting materials in 33% yield.  

Leave a Comment