Reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[Br:13][C:14]1[CH:19]=[C:18]([F:20])[C:17]([F:21])=[CH:16][C:15]=1[F:22].C([N-]C(C)C)(C)C.[Li+].[CH3:31][Si:32](Cl)([CH3:34])[CH3:33].FC(F)(F)S(OC)(=O)=O>O1CCCC1.CCOCC>[Br:13][C:14]1[CH:19]=[C:18]([F:20])[C:17]([F:21])=[C:16]([Si:32]([CH3:34])([CH3:33])[CH3:31])[C:15]=1[F:22]Participants
Reactant 6
Product 1
Reagents, catalysts & solvents 2
Procedure
This preparation route is very expensive. The first and the second synthesis step each involve reaction with butyllithium and diisopropylamine in tetrahydrofuran at −78° C., and the third synthesis step involves reaction with butyllithium in ether, likewise at −78° C. In the first step, 1-bromo-2,4,5-trifluorobenzene is reacted first with lithium diisopropylamide and then with trimethylsilyl chloride, the resulting 1-bromo-2,4,5-trifluoro-3-(trimethylsilyl)benzene (88% yield) is once more reacted with lithium diisopropylamide and subsequently with methyl trifluoromethanesulfonate, the resulting 1-bromo-2,4,5-trifluoro-6-methyl-3-(trimethylsilyl)benzene (75% yield) is reacted with butyllithium and subsequently with CO2 in the form of dry ice, and the resulting 2,4,5-trifluoro-6-methyl-3-(trimethylsilyl)- benzoic acid (62% yield) is reacted with cesium fluoride in acetonitrile to give 6-methyl-2,4,5-trifluorobenzoic acid (89% yield).
Workup
- customThe first and the second synthesis step
- customthe third synthesis step
- customlikewise at −78° C
Sources & evidence
- ORD record
- ord-8831a9dd4b444a58ab4d19325cb20e76
- Source dataset
- uspto-grants-2002_03
- Patent number
- US06362365B1
Linked notes
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