Toluene → HCID 86702139, compound

HRID 1776201Notes

Reaction equation

HRID 1776201 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][CH:3]=1.[Cl:9][C:10]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:11]=1[NH2:12].C1(C)C=CC=CC=1.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.O>[Cl:9][C:10]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:11]=1[NH:12][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 99931-Bromo-4-fluorobenzeneHCID 27365092-Chloro-5-fluoroanilineHCID 23676156Sodium t-butoxide

Product 1

HCID 86702139HCID 86702139, compoundYield 87.2%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

A round bottom flask was charged with 1-bromo-4-fluorobenzene (4.809 g, 27.5 mmol), 2-chloro-5-fluoroaniline (4.000 g, 27.5 mmol), Xantphos (0.636 g, 1.1 mmol), anhydrous toluene (100 mL), and sodium tert-butoxide (3.961 g, 41.2 mmol). The mixture was degassed and filled with argon, and then tris(dibenzylideneacetone)dipalladium(0) (0.755 g, 0.8 mmol) was added and the reaction was stirred under argon at 110° C. for 5 hrs. After cooling to room temperature, the mixture was treated with water and extracted with diethyl ether. The organic layer was washed with saturated aqueous sodium chloride, dried (anhydrous magnesium sulfate), filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (0-20% ethyl acetate/hexanes) to afford the product as a colorless oil (5.75 g, 87%). 1H NMR (300 MHz, CDCl3) δ 7.27 (dd, 1H, J=9.0, 5.4 Hz), 7.23-7.03 (m, 4H), 6.71 (dd, 1H, J=10.8, 2.4 Hz), 6.47 (td, 1H, J=8.1, 3.0 Hz), 6.09 (br s, 1H).

Workup

  1. customThe mixture was degassed
  2. additionfilled with argon
  3. temperatureAfter cooling to room temperature
  4. extractionextracted with diethyl ether
  5. washThe organic layer was washed with saturated aqueous sodium chloride
  6. dry with materialdried (anhydrous magnesium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by silica gel chromatography (0-20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-f343d175a2254c5ba688914a8bc6aac5
Source dataset
uspto-grants-2016_02
Patent number
US09265772B2

Reaction notes

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