DICHLOROMETHANE AS REACTANT IN SYNTHESIS - AN EXPEDIENT TRANSFORMATION OF PROLINAMIDE TO A NOVEL PYRROLO[1,2-C]IMIDAZOLONE

In the course of our work to achieve an efficient production method for the neuroleptic drug remoxipride (l), 2,3we have been developing a new synthetic route for (S)-2-(aminomethyl)-l-ethylpyrrolidine (2), a crucial building block for 1 and for other pharmacologically interesting compounds.4Our favored synthesis5of 2 starts (S)-proline (3)6 and proceeds in a virtually stereoconser vative7 fashion according to Scheme I. On certain occa sions, especially when running large-scale experiments (e.g. in the pilot plant), we noted the formation of 3-4% (GC) of an impurity in the transformation of ester 4 to amide 5. We now present the structure elucidation of the by-product as 6 and a mechanistic proposal for its formation. © 1990, American Chemical Society. All rights reserved.