m-Toluidine → N-(3-(1,3-dioxolan-2-yl)phenyl)-3-methylaniline

HRID 42393

Reaction equation

HRID 42393 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[CH:3]=1.Br[C:10]1[CH:11]=[C:12]([CH:16]2[O:20][CH2:19][CH2:18][O:17]2)[CH:13]=[CH:14][CH:15]=1.CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[O:17]1[CH2:18][CH2:19][O:20][CH:16]1[C:12]1[CH:11]=[C:10]([NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[CH:3]=2)[CH:15]=[CH:14][CH:13]=1

Participants

7

Reactant 4

HCID 7934m-ToluidineHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 873062-(3-Bromophenyl)-1,3-dioxolaneHCID 23676156Sodium t-butoxide

Product 1

HCID 58028482N-(3-(1,3-dioxolan-2-yl)phenyl)-3-methylaniline

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

To a clean and dry 500 ml round bottom flask equipped with a reflux condenser and magnetic stir bar nitrogen was purged and anhydrous toluene (250.0 ml) was added by cannula. m-toluidine (5.1 ml, 0.0467 mol) was added to the reaction flask by syringe. Next, 2-(3-bromophenyl)-1,3-dioxolane (7.8 ml, 0.0513 mol) was added by syringe. The reaction solution was purged with a strong nitrogen flow for 30 minutes. Sodium tert-butoxide (6.73 g, 0.0701 mol) and Pd2dba3 (0.85 g, 0.0009 mol) were then added manually, followed by the addition of tri-tert-butylphosphine (0.57 g, 0.0028 mol) in toluene (˜8 ml) via syringe. The vessel was heated to reflux for approximately 4 hours. The reaction was then cooled to room temperature and filtered through a Celite and silica gel pad. Solvent was removed by rotary evaporation. The crude material was partially dissolved in a 10% ethyl acetate/hexane solution (20.0 ml) and purified by flash column chromatography providing near pure product. Further purification was carried out using an automatic column chromatography system using 5% ethyl acetate/hexane as an eluent. This provided pure product confirmed by NMR.

Workup

  1. customTo a clean and dry 500 ml round bottom flask
  2. customequipped with a reflux condenser and magnetic stir bar nitrogen
  3. customwas purged
  4. additionanhydrous toluene (250.0 ml) was added by cannula
  5. customThe reaction solution was purged with a strong nitrogen flow for 30 minutes
  6. temperatureThe vessel was heated
  7. temperatureto reflux for approximately 4 hours
  8. filtrationfiltered through a Celite and silica gel pad
  9. customSolvent was removed by rotary evaporation
  10. dissolutionThe crude material was partially dissolved in a 10% ethyl acetate/hexane solution (20.0 ml)
  11. custompurified by flash column chromatography
  12. customproviding near pure product
  13. customFurther purification

Sources & evidence

ORD record
ord-87c6982c816849e0afb91516c2992a69
Source dataset
uspto-grants-2013_09
Patent number
US08535974B2

Linked notes

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