Sodium Carbonate → 4-Bromo-3',5'-dimethoxy-biphenyl-2,3-diamine

HRID 43111

Reaction equation

HRID 43111 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.[Br:14][C:15]1[CH:20]=[CH:19][C:18](Br)=[C:17]([NH2:22])[C:16]=1[NH2:23].C([O-])([O-])=O.[Na+].[Na+]>CCO.C1(C)C=CC=CC=1.CCOC(C)=O.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Br:14][C:15]1[CH:20]=[CH:19][C:18]([C:5]2[CH:4]=[C:3]([O:2][CH3:1])[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=2)=[C:17]([NH2:22])[C:16]=1[NH2:23]

Participants

9

Reactant 3

HCID 10340Sodium CarbonateHCID 4374257(3,5-Dimethoxyphenyl)boronic acidHCID 118215323,6-Dibromobenzene-1,2-diamine

Product 1

HCID 592928784-Bromo-3',5'-dimethoxy-biphenyl-2,3-diamineYield 37.9%

Reagents, catalysts & solvents 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of 3,5-dimethoxyphenylboronic acid (15.1 g, 82.7 mmol, 1.1 equiv) (Step 1.8) in EtOH (50 mL) was added dropwise to a mixture of 3,6-dibromo-benzene-1,2-diamine (20 g, 75.2 mmol) (Step 1.6), PdCl2(dppf) (6.1 g, 7.5 mmol, 0.1 equiv), Na2CO3 (2 M solution in H2O, 150 mL, 300.8 mmol, 4 equiv) in toluene (300 mL) at 105° C., under an argon atmosphere. The reaction mixture was stirred at 105° C. for 3 h, allowed to cool to rt, diluted with EtOAc and H2O and extracted with EtOAc. The organic phase was washed with H2O and brine, dried (Na2SO4), filtered and concentrated. The crude product was purified by silica gel column chromatography (DCM) followed by trituration in EtOH to afford 9.2 g of the title compound as a white solid: ES-MS: 323.0/325.0 [M+H]+; tR=4.43 min (System 1); Rf=0.15 (DCM).

Workup

  1. temperatureto cool to rt
  2. extractionextracted with EtOAc
  3. washThe organic phase was washed with H2O and brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by silica gel column chromatography (DCM)

Sources & evidence

ORD record
ord-99b0390f550b43afa7312b65ce2d7fbd
Source dataset
uspto-grants-2013_09
Patent number
US08536175B2

Linked notes

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