A novel process for the preparation of [(R,S)/ (S,R)] and [(S,S)/ (R,R)] chroman epoxides, key intermediates in the synthesis of Nebivolol

A novel, cost effective, scalable process for the preparation of chroman epoxides starting from 4-fluorophenol is described. The highlights of the process are single step O -acylation, fries rearrangement, one pot synthesis of claisen condensation, cyclization, reduction, epoxidation with over all yield of 50.9% [( R , S )/( S , R )]-chroman epoxide-A is 33.9% and [( S , S )/( R , R )]-chroman epoxide-B is 17%.