Benzophenone → 3-tert-Butoxy-5-fluoroaniline

HRID 658335Notes

Reaction equation

HRID 658335 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH:3]=1.C(C1C=CC=CC=1)(=O)C1C=CC=CC=1.C[O-].[Na+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC([O-])=O.[Na+].Cl.[NH2:83]O>C1(C)C=CC=CC=1.CO>[C:10]([O:9][C:4]1[CH:3]=[C:2]([NH2:83])[CH:7]=[C:6]([F:8])[CH:5]=1)([CH3:13])([CH3:12])[CH3:11]

Participants

9

Reactant 6

HCID 3102BenzophenoneHCID 443297Hydroxyamine hydrochlorideHCID 517045Sodium AcetateHCID 634876Binap, (A+-)-HCID 10942334Sodium MethoxideHCID 568442921-Bromo-3-tert-butoxy-5-fluorobenzene

Product 1

HCID 667439143-tert-Butoxy-5-fluoroaniline

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

1-Bromo-3-tert-butoxy-5-fluorobenzene (56.1 g), benzophenone (50.9 g), NaOMe (50.5 g) and 2,2′-Bis-diphenylphosphanyl-[1,1′]binaphthalenyl (17.5 g) are dissolved in toluene (500 ml). The reaction mixture is flushed with argon, Pd2(dba)3 (5.4 g) is added and the reaction mixture is heated to 80° C. for 40 hours. The reaction mixture is quenched with water. The organics are separated, dried over MgSO4, filtered and the solvent removed in vacuo. The intermediate is obtained by flash column chromatography (silica, eluent dichloromethane). The resulting product is then dissolved in MeOH (1 L). NaOAc (46.1 g), hydroxylamine hydrochloride (29.1 g) are added and the reaction mixture is stirred at room temperature for 2.5 hours. The reaction mixture is quenched with 0.1M NaOH, extracted into DCM (2×), dried over MgSO4, filtered and the solvent removed in vacuo to give the title compound. 1H nmr (CDCl3, 400 MHz); 6.20 (m, 3H), 3.75 (br s, 2H), 1.4 (s, 9H).

Workup

  1. customThe reaction mixture is flushed with argon, Pd2(dba)3 (5.4 g)
  2. additionis added
  3. customThe reaction mixture is quenched with water
  4. customThe organics are separated
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customthe solvent removed in vacuo
  8. customThe intermediate is obtained by flash column chromatography (silica, eluent dichloromethane)
  9. customThe reaction mixture is quenched with 0.1M NaOH
  10. extractionextracted into DCM (2×)
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-b39c6c4777ea4c5a9cb839923abbe3c1
Source dataset
uspto-grants-2011_12
Patent number
US08076489B2

Reaction notes

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