THE SUPERBASE APPROACH TO FLURBIPROFEN - AN EXERCISE IN OPTIONALLY SITE-SELECTIVE METALATION

A superior route to the analgesic flurbiprofen has been devised. Key s teps are the selective deprotonation of 3-fluorotoluene with tert-buty llithium in the presence of potassium tert-butoxide (LIT-KOR) at the 4 -position and the selective deprotonation of the 4-methyl-2-fluorobiph enyl with lithium diisopropylamide in the presence of potassium tert-b utoxide (LIDA-KOR) at the benzylic position. Depending on the reagent and the substituent pattern, the 3- and 5-positions of 2-fluorobipheny ls can also be specifically attacked.