A one-pot synthesis of ibuprofen involving three consecutive steps of superbase metalation

A one-pot reaction sequence consisting of three consecutive metalation and electrophilic substitution stages starting with p-xylene leads to 2-(4-isobutylphenyl)propanoic acid with a 52% overall yield. A crucial step is the alkylation of deprotonated p-ethyltoluene with isopropyl bromide. In general terms, sec-alkyl halides and benzyl- or allyl-type alkali metal reagents undergo coupling reactions with surprising ease. [on SciFinder (R)]


Published in:
Tetrahedron Letters, 32, 28, 3369-70
Year:
1991
Keywords:
Note:
CAN 115:158648
25-17
Benzene, Its Derivatives, and Condensed Benzenoid Compounds
Inst. Chim. Org.,Univ. Lausanne,Lausanne,Switz.
Journal
0040-4039
written in English.
2785-29-7 (Benzylpotassium) Role: RCT (Reactant), RACT (Reactant or reagent) (benzylation by, of bromopentane); 108-85-0 (Cyclohexylbromide); 1809-10-5 (3-Bromopentane) Role: RCT (Reactant), RACT (Reactant or reagent) (benzylation of); 78-76-2 Role: RCT (Reactant), RACT (Reactant or reagent) (condensation of, with butenylpotassium); 136295-05-1 Role: RCT (Reactant), RACT (Reactant or reagent) (condensation of, with sec-Bu bromide); 622-96-8P (4-Ethyltoluene) Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. and sequential regioselective metalation-alkylation of); 100319-40-2P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. and sequential regioselective metalation-carboxylation of); 1553-60-2P (4-Isobutylphenylacetic acid); 3585-52-2P; 4410-75-7P (Benzylcyclohexane); 15687-27-1P; 16745-94-1P (3,4-Dimethyl-1-hexene); 19219-85-3P (3-Benzylpentane); 24608-84-2P ((Z)-5-Methyl-2-heptene) Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of); 106-42-3 (p-Xylene) Role: RCT (Reactant), RACT (Reactant or reagent) (regioselective metalation-alkylation of); 105-05-5 (p-Diethylbenzene); 5161-04-6 (p-Isobutyltoluene) Role: RCT (Reactant), RACT (Reactant or reagent) (regioselective metalation-carboxylation of)
Laboratories:




 Record created 2006-03-03, last modified 2018-12-03


Rate this document:

Rate this document:
1
2
3
 
(Not yet reviewed)