2,4-Difluoroaniline → [2-Chloro-4-(2,4-difluoro-phenylamino)-phenyl]-(2-methyl-5-nitro-phenyl)-methanone

HRID 1012609

Reaction equation

HRID 1012609 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[CH:13]=[CH:12][C:11]=2[CH3:19])=[O:9])=[C:4]([Cl:20])[CH:3]=1.[F:21][C:22]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:23]=1[NH2:24].C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2].CCOC(C)=O.O>[Cl:20][C:4]1[CH:3]=[C:2]([NH:24][C:23]2[CH:25]=[CH:26][C:27]([F:29])=[CH:28][C:22]=2[F:21])[CH:7]=[CH:6][C:5]=1[C:8]([C:10]1[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[CH:13]=[CH:12][C:11]=1[CH3:19])=[O:9]

Participants

9

Reactant 4

HCID 97092,4-DifluoroanilineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 11494123(4-Bromo-2-chloro-phenyl)-(2-methyl-5-nitro-phenyl)-methanone

Product 1

HCID 11618303[2-Chloro-4-(2,4-difluoro-phenylamino)-phenyl]-(2-methyl-5-nitro-phenyl)-methanone

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Compound 492 (5.4 g, 15.2 mmol) was dissolved in dry 1,4-dioxan (150 mL) in a 200 mL screw cap vessel. 2,4-Difluoroaniline (1.7 mL, 16.7 mmol) was added and argon was blown over the mixture. Cs2CO3 (14.9 g, 45.7 mmol), BINAP (0.38 g, 0.6 mmol) and Pd(OAc)2 (0.14 g, 0.6 mmol) were added and argon was blown through the mixture and the screw cap vessel was closed. The mixture was stirred at 100° C. for 7 h. The reaction mixture was poured into H2O (100 mL) and EtOAc (200 mL). The water phase was extracted with EtOAc (×3) and the combined organic phases were washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by flash chromatography using CH2Cl2/petroleum ether (40-60) 2:3→1:1→1:0 followed by EtOAc as the eluent to afford the title compound as a yellow crystalline compound.

Workup

  1. customscrew cap vessel
  2. customthe screw cap vessel
  3. customwas closed
  4. extractionThe water phase was extracted with EtOAc (×3)
  5. washthe combined organic phases were washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-769df04fde574f98aa7bded2a81404cd
Source dataset
uspto-grants-2011_07
Patent number
US07977387B2

Linked notes

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