Hydrochloric Acid → 3-Chloro-2,4-difluorobenzoic acid
Reaction equation
C([Li])CCC.CN(C)CCN(C)C.[F:14][C:15]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:16]=1[C:17]([OH:19])=[O:18].[Cl:25]C(Cl)(Cl)C(Cl)(Cl)Cl.Cl>CCCCCC.O1CCCC1.O>[F:14][C:15]1[C:23]([Cl:25])=[C:22]([F:24])[CH:21]=[CH:20][C:16]=1[C:17]([OH:19])=[O:18]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- -70 °C
Procedure
294 ml (0.471 mol) of a 1.6N solution of n-butyllithium in hexane are added dropwise and at -70° C. to a solution of 71 ml (0.471 mol) of tetramethylethylenediamine (TMEDA) in 300 ml of dry tetrahydrofuran (THF). 33.8 g (0.214 mol) of 2,4-difluorobenzoic acid, in 100 ml of dry tetrahydrofuran (THF), are added dropwise with stirring, under argon and at -70° C., to the above solution. After stirring for one hour, 111.5 g (0.471 mol) of hexachloroethane in solution in 150 ml of dry THF are run in. After two hours at -70° C., the temperature is allowed to return to 10° C. The reaction mixture is hydrolysed with 150 ml of ice-cooled water and brought to a pH of approximately 1 by addition of 3N hydrochloric acid. The aqueous phase is extracted with ether, dried over magnesium sulphate and concentrated. The residue is recrystallised from heptane/ether. 16.5 g (yield 40%) of 2,4-difluoro-3-chlorobenzoic acid are obtained.
Workup
- stirringAfter stirring for one hour
- customto return to 10° C
- extractionThe aqueous phase is extracted with ether
- dry with materialdried over magnesium sulphate
- concentrationconcentrated
- customThe residue is recrystallised from heptane/ether
Sources & evidence
- ORD record
- ord-f1edba8f7f994e24ae5b665917c7fd0b
- Source dataset
- uspto-grants-1999_08
- Patent number
- US05945382
Reaction notes
Loading…