3-Bromoaniline → 3-(3,5-Dimethylphenyl)aniline

HRID 1365096Notes

Reaction equation

HRID 1365096 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].[CH3:9][C:10]1[CH:11]=[C:12](B(O)O)[CH:13]=[C:14]([CH3:16])[CH:15]=1.[F-].[Cs+]>C1COCC1.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].P(C(C)(C)C)(C(C)(C)C)C(C)(C)C>[CH3:9][C:10]1[CH:11]=[C:12]([C:2]2[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=2)[NH2:5])[CH:13]=[C:14]([CH3:16])[CH:15]=1

Participants

7

Reactant 3

HCID 115623-BromoanilineHCID 25953Cesium fluorideHCID 27343493,5-Dimethylphenylboronic acid

Product 1

HCID 121662363-(3,5-Dimethylphenyl)anilineYield 99%

Reagents, catalysts & solvents 3

HCID 83681Tris(1,1-dimethylethyl)phosphineCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-bromoaniline, 8, (17.2 g, 0.10 mol), 3,5-dimethylphenylboronic acid (16.5 g, 0.11 mol), CsF (50 g, 0.33 mol), Pd2(dba)3 (0.92 g, 5 mmol) in 50 mL anhydrous THF was added a solution of P(t-Bu)3 (0.49 g, 2.4 mmol) in 3 mL of THF. The exothermal reaction was cooled using a water bath. The solution mixture was stirred at room temperature for 2 hours and concentrated in vacuo. The residue was dissolved in methylene chloride and washed with water. The combined organic layers were dried over MgSO4 and solvents were evaporated. Purification of the orange residue by flash chromatography (100:10:1 hexanes:ethyl acetate:triethylamine) afforded 9 (20.0 g, 99%) as a brown oil. 1H-NMR δ=2.30 (s, 6H), 3.53 (bs, 2H), 6.50 (dd, J=2.5 Hz, 7.1 Hz, 1H), 6.77 (d, J=1.6 Hz, 2.2 Hz, 1M), 6.91 (s, 1H), 6.94 (dd, J=1.2 Hz, 2.5 Hz, 1H), 7.10-7.15 (m, 3H). 13C-NMR δ=22.2, 115.4, 119.3, 125.7, 129.5, 130.2, 138.7, 141.8, 143.3, 145.7. Anal. calcd. for C14H15N: C, 85.28; H, 7.61; N, 7.11. Found: C, 85.61; H, 8.01; N, 7.00.

Workup

  1. customThe exothermal reaction
  2. temperaturewas cooled
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in methylene chloride
  5. washwashed with water
  6. dry with materialThe combined organic layers were dried over MgSO4 and solvents
  7. customwere evaporated
  8. customPurification of the orange residue by flash chromatography (100:10:1 hexanes:ethyl acetate:triethylamine)

Sources & evidence

ORD record
ord-2131d1a77ebc4d6494f5defeb8f2bb06
Source dataset
uspto-grants-2011_02
Patent number
US07888509B2

Reaction notes

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