Bromobenzene → 3-Fluorodiphenylamine

HRID 341365Notes

Reaction equation

HRID 341365 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].Br[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH:5][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

6

Reactant 3

HCID 7961BromobenzeneHCID 97423-FluoroanilineHCID 23676156Sodium t-butoxide

Product 1

HCID 27744663-FluorodiphenylamineYield 0.1%

Reagents, catalysts & solvents 2

HCID 53485975CID 53485975CatalystHCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

In a 3 liter, three-neck flask equipped with mechanical stirring, a solution of 3-fluoroaniline (75 g, 675 mol), bromobenzene (73 mL, 690 mol), and dichloro[1,1′-bis(diphenylphosphino)-ferrocene]palladium(II) dichloromethane adduct (15 g, 18 mmol) in anhydrous toluene (1.3 L) containing sodium tert-butoxide (130 g, 1.35 mol) was heated at 105° C. for 3 h. The reaction mixture was then cooled to 80° C., and then quenched by gradually pouring the reaction mixture into ice water (1 L). The aqueous layer was removed, and was then extracted with an additional volume of toluene (300 mL). The organic extracts were combined, rinsed with brine, dried over MgSO4, and passed through a silica plug (1.3 kg), eluting with toluene. The solvent was removed to give a dark amber oil (86 g). LCMS m/z (%)=188.0 [M+H]+; 1H NMR (400 MHz, CDCl3) δ 6.45 (t, J=8.5 Hz, 1H), 6.62-6.66 (m, 2H), 6.87 (t, J=7.2 Hz, 1H), 6.98 (d, J=7.6 Hz, 2H), 7.05 (q, J=7.5 Hz, 1H), 7.17 (t, J=8.6 Hz, 2H).

Workup

  1. customIn a 3 liter, three-neck flask equipped with mechanical stirring
  2. temperatureThe reaction mixture was then cooled to 80° C.
  3. customquenched
  4. additionby gradually pouring the reaction mixture into ice water (1 L)
  5. customThe aqueous layer was removed
  6. extractionwas then extracted with an additional volume of toluene (300 mL)
  7. washrinsed with brine
  8. dry with materialdried over MgSO4
  9. washeluting with toluene
  10. customThe solvent was removed

Sources & evidence

ORD record
ord-6ad44ec2860140499cb777da03b6878a
Source dataset
uspto-grants-2014_11
Patent number
US08895776B2

Reaction notes

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