Oxalyl chloride → N-(2-bromo-4-(perfluoropropan-2-yl)-6-(trifluoromethyl)phenyl)-4-cyano-2,3-difluorobenzamide

HRID 590926Notes

Reaction equation

HRID 590926 reaction equation
[C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[C:5]([F:12])[C:4]=1[F:13])#[N:2].C(Cl)(=O)C(Cl)=O.C(C1C=CC(C(Cl)=O)=C(F)C=1F)#N.[Br:33][C:34]1[CH:40]=[C:39]([C:41]([F:50])([C:46]([F:49])([F:48])[F:47])[C:42]([F:45])([F:44])[F:43])[CH:38]=[C:37]([C:51]([F:54])([F:53])[F:52])[C:35]=1[NH2:36]>ClCCl.CN(C=O)C.CN1C(=O)N(C)CC1.C(OCC)(=O)C.O>[Br:33][C:34]1[CH:40]=[C:39]([C:41]([F:50])([C:42]([F:44])([F:45])[F:43])[C:46]([F:47])([F:49])[F:48])[CH:38]=[C:37]([C:51]([F:52])([F:53])[F:54])[C:35]=1[NH:36][C:7](=[O:9])[C:6]1[CH:10]=[CH:11][C:3]([C:1]#[N:2])=[C:4]([F:13])[C:5]=1[F:12]

Participants

10

Reactant 4

HCID 65578Oxalyl chlorideHCID 582975582-Bromo-4-(1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl)-6-(trifluoromethyl)benzenamineHCID 592269714-Cyano-2,3-difluorobenzoic acidHCID 866542544-Cyano-2,3-difluorobenzoyl chloride

Product 1

HCID 86654253N-(2-bromo-4-(perfluoropropan-2-yl)-6-(trifluoromethyl)phenyl)-4-cyano-2,3-difluorobenzamideYield 27%

Reagents, catalysts & solvents 5

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 66611,3-Dimethyl-2-imidazolidinoneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 0.840 g (4.59 mmol) of 4-cyano-2,3-difluorobenzoic acid in 10 ml of dichloromethane were added one drop of DMF and 0.470 ml (5.51 mmol) of oxalyl chloride, followed by stirring at room temperature for 1 hour. The solvent was evaporated under reduced pressure and the obtained 4-cyano-2,3-difluorobenzoyl chloride was added to a solution of 1.56 g (3.83 mmol) of 2-bromo-4-(perfluoropropan-2-yl)-6-(trifluoromethyl)aniline obtained in 1-2 of Example 1 in 5 ml of DMI, followed by stirring at 130° C. for 5 hours. To the reaction liquid were added water and ethyl acetate, and the organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel column chromatography (eluent solvent; hexane:ethyl acetate=1:0→10:1) to prepare 0.58 g (yield 27%) of a target compound.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. stirringby stirring at 130° C. for 5 hours
  3. customTo the reaction liquid
  4. washthe organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customthe obtained residue was purified by silica gel column chromatography (eluent solvent; hexane:ethyl acetate=1:0→10:1)

Sources & evidence

ORD record
ord-4f64f82865704069866a569a68536290
Source dataset
uspto-grants-2016_01
Patent number
US09237745B2

Reaction notes

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