Use a dicyclohexylamine salt to crystallise a carboxylic acid and upgrade compound purity

15 October 2004

Some carboxylic acids can be difficult or slow to crystallise. Dicyclohexylamine (DCA) often forms good crystalline salts with carboxylic acids allowing the purity of the acid to be upgraded by crystallisation. A recent example uses this technique to crystallise a substituted chiral succinic acid. Asymmetric hydrogenation of the substituted itaconic shown below proceeded efficiently using ruthenium BINAP as catalyst giving the succinic acid in 80-85% yield, 90-95% ee. However the succinic acid would not easily crystallise. Various salts were examined (Na, K, Mg, Et3N etc.) but recrystallisation of the DCA salt proved to be the most consistent method, upgrading chemical purity from 95 to >99% and ee from 94% to >99%. As an extra development it was found that DCA could be added to the hydrogenation reaction and the crude DCA salt isolated from precipitation of the reaction mixture was generally >98% chemically pure and 98% enantiomerically pure.

M.D. Wallace et al., Org. Process Res. Dev., 2004, 8(5), 738.