Acetic Anhydride → 3-Methyl-4-(4,4,4-trifluoro-1-((4-(methoxycarbonyl)phenyl)amino)butyl)benzoic acid

HRID 1520285Notes

Reaction equation

HRID 1520285 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:15][C:16]2[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][CH:17]=2)[CH2:9][CH2:10][C:11]([F:14])([F:13])[F:12])=[C:4]([CH3:26])[CH:3]=1.C(N(CC)C(C)C)(C)C.[C:36]([O-:39])(=[O:38])C.[Li+].C(OC(=O)C)(=O)C>O.CN(C=O)C>[CH3:26][C:4]1[CH:3]=[C:2]([CH:7]=[CH:6][C:5]=1[CH:8]([NH:15][C:16]1[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][CH:17]=1)[CH2:9][CH2:10][C:11]([F:14])([F:13])[F:12])[C:36]([OH:39])=[O:38]

Participants

7

Reactant 4

HCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 3474584Lithium acetateHCID 117840148Methyl 4-((1-(4-bromo-2-methylphenyl)-4,4,4-trifluorobutyl)amino)benzoate

Product 1

HCID 1178400353-Methyl-4-(4,4,4-trifluoro-1-((4-(methoxycarbonyl)phenyl)amino)butyl)benzoic acidYield 52.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

Under a nitrogen atmosphere, to a mixture of methyl 4-((1-(4-bromo-2-methylphenyl)-4,4,4-trifluorobutyl)amino)benzoate (racemate) (1.5 g), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (0.285 g), N,N-diisopropylethylamine (3.65 mL), lithium acetate 2 hydrate (2.85 g) and DMF (17 mL) was added acetic anhydride (1.977 mL), and the mixture was stirred at 120° C. overnight. To the reaction mixture was added water at room temperature, and the insoluble material was filtered off through celite. The filtrate was extracted with ethyl acetate, and the extract was washed with 1M hydrochloric acid and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (725.6 mg).

Workup

  1. filtrationthe insoluble material was filtered off through celite
  2. extractionThe filtrate was extracted with ethyl acetate
  3. washthe extract was washed with 1M hydrochloric acid and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-a7e831950aec4eea8a0bfb389a05ec60
Source dataset
uspto-grants-2015_07
Patent number
US09073864B2

Reaction notes

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