Synthesis of β-tetralones on a large scale

We constantly have a need for the synthesis of different β-tetralones on a large scale for use in the multi-step synthesis of Active Pharmaceutical Ingredients.

Posted: January 7, 2016

API Manufacturing and Pharmaceutical Manufacturing

Several of these tetralones are not stable and thus need to be isolated cold and often as a bisulfite adduct which are then converted to the corresponding tetralone before being used in the next step. The conversion of phenylacetic acid chlorides to 2- tetralones with ethylene under Friedel-Crafts conditions is well known in the literature. The typical process involves adding ethylene gas to a mixture of phenylacetyl chloride and AlCl3 at -20 to 0 °C which usually gives the Tetralone as an oily semi-solid in less than 50% yield. After considerable study, the temperature and the dispersion rate at which ethylene was added was found to be the key to producing crystalline tetralones with acceptable purity. In order to prevent polyethylene formation, the stoichiometry of ethylene is also very critical to the process. After additional development and extensive optimization, we have been able to scale up the synthesis of various β-tetralones to 100 kg scale with excellent reproducilibilty in terms of yield (> 70 %) and purity (95 %-98 %).

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About the Author

Ed Price CEO of PCI Synthesis
Ed is the President and CEO of PCI Synthesis (PCI), he serves as a co-chair of the New England CRO/CMO Council and sits on the Industrial Advisory Board for the Department of Chemical Engineering at UMass, Amherst. Ed is also a long standing member of the American Chemical Society and advises the Bulk Pharmaceutical Task Force of the Society of Chemical Manufacturer’s and Affiliates (SOCMA).

Do you have questions? Talk to Ed.