One-pot synthesis of procaine and other pharmaceuticals

ORGN 126

Hong Yang, The National Centre for Upgrading Technology, 1 Oil patch Drive, Devon, AB T9J 1A8, Canada and Fernand C. Thyrion, Chemical Engineering Institute, Louvain University, Voie Minckelers 1, 1348 Louvain-la Neuve, Belgium.
Procaine is used as local anesthetic since 1909 and is still being used currently. Several methods have been reported to make procaine. For examples: the reaction of 4-nitrobenzoyl chloride with 2-diethylaminoethanol followed by the reduction of 2-ethylaminoethyl-4-nitrobenzoate to 4-aminobenzoate, esterification of 4-aminobenzonic acid with 2-ethylaminoethanol in the presence of H2SO4 and the reaction of 4-aminobenzonic acid with 2-chloroethyldiethylamine. All these methods require more than one step to reach the final product. This work presents an innovative process that leads to one-pot synthesis of procaine and other useful pharmaceuticals. 93% selectivity on procaine can be obtained under our optimized condition. Other pharmaceuticals such as adiphenine and drofenine could also be synthesized in one-pot using this novel process.