The superbase approach to flurbiprofen: an exercise in optionally site-selective metalation
A superior route to the analgesic flurbiprofen has been devised. Key steps are the selective deprotonation of 3-fluorotoluene with tert-butyllithium in the presence of potassium tert-butoxide (LIT-KOR) at the 4-position and the selective deprotonation of the 4-methyl-2-fluorobiphenyl with lithium diisopropylamide in the presence of potassium tert-butoxide (LIDA-KOR) at the benzylic position. Depending on the reagent and the substituent pattern, the 3- and 5-positions of 2-fluorobiphenyls can also be specifically attacked. [on SciFinder (R)]
1998
4
10
1969
1973
CAN 130:38170 25-17 Benzene, Its Derivatives, and Condensed Benzenoid Compounds Institut de Chimie organique de l'Universite Batiment de Chimie,Lausanne-Dorigny,Switz. Journal 0947-6539 written in English. 216701-21-2P; 216701-23-4P; 216701-24-5P; 216701-27-8P; 216701-28-9P; 216701-30-3P; 216701-33-6P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of); 352-70-5 (3-Fluorotoluene) Role: RCT (Reactant), RACT (Reactant or reagent) (super base approach to flurbiprofen via regioselective metalation); 5001-96-7P; 7697-23-6P; 69168-29-2P; 170981-26-7P; 216701-22-3P; 216701-25-6P; 216701-26-7P; 216701-29-0P; 216701-31-4P; 216701-32-5P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (super base approach to flurbiprofen via regioselective metalation); 5104-49-4P (Flurbiprofen) Role: SPN (Synthetic preparation), PREP (Preparation) (super base approach to flurbiprofen via regioselective metalation)
REVIEWED
EPFL