Diisopropylamine → 2-(2,4-Difluoroanilino)-4,5-difluorobenzoic acid
Reaction equation
C([N-]C(C)C)(C)C.[Li+].C(NC(C)C)(C)C.C([Li])CCC.[F:21][C:22]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:23]=1[NH2:24].F[C:31]1[CH:39]=[C:38]([F:40])[C:37]([F:41])=[CH:36][C:32]=1[C:33]([OH:35])=[O:34].Cl.O1CCOCC1>C1COCC1>[F:21][C:22]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:23]=1[NH:24][C:31]1[CH:39]=[C:38]([F:40])[C:37]([F:41])=[CH:36][C:32]=1[C:33]([OH:35])=[O:34]Participants
8
Reactant 6
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -78 °C
Procedure
Lithium diisopropylamide was generated at −5° C. by combining diisopropylamine (7.2 mL, 51 mmol) and n-butyl lithium (33 mL, 53 mmol) in 150 mL of dry THF. After 30 minutes, the solution was cooled to −78° C. and 2,4-difluoroaniline (3.46 mL, 34 mmol) was added and stirred for 2 hours. 2,4,5-Trifluorobenzoic acid (3.0 g, 17 mmol) was added, and the mixture was allowed to warm to room temperature over 17 hours. A saturated solution of HCl/dioxane (10 mL) was added, and after 1 hour the mixture was concentrated to a solid. The solid was redissolved in chloroform and washed with 1N HCl, water, and brine. The solution was dried and concentrated to afford 4.54 g of the title compound as a solid.
Workup
- customwas generated at −5° C.
- temperatureto warm to room temperature over 17 hours
- concentrationafter 1 hour the mixture was concentrated to a solid
- dissolutionThe solid was redissolved in chloroform
- washwashed with 1N HCl, water, and brine
- customThe solution was dried
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-c668f560998c498c8a78084dd6848b98
- Source dataset
- uspto-grants-2004_11
- Patent number
- US06825199B2
Reaction notes
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