Development of an SNAr Reaction: A Practical and Scalable Strategy to Sequester and Remove HF

A simple and operationally practical method to sequester and remove fluoride generated through the SNAr reaction between amines and aryl fluorides is reported. Calcium propionate acts as an inexpensive and environmentally benign in situ scrubber of the hydrofluoric acid byproduct, which is simply precipitated and filtered from the reaction mixture during standard aqueous work-up. The method has been tested from 10 → 100 g scale of operation, showing > 99.5% decrease in fluoride content in each case. Full mass recovery of calcium fluoride is demonstrated at both scales, proving this to be a general, efficient and robust method of fluoride abstraction to help prevent corrosion of glass-lined reactors.