Toluene → Methyl 2-amino-5-phenylbenzoate

HRID 1976109Notes

Reaction equation

HRID 1976109 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[C:8](Br)[CH:7]=[CH:6][C:5]=1[NH2:11].[C:13]1(C)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(B(O)O)C=CC=CC=1>CO.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3]([C:4]1[CH:9]=[C:8]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:7]=[CH:6][C:5]=1[NH2:11])=[O:12]

Participants

8

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 736224Methyl 2-amino-5-bromobenzoate

Product 1

HCID 16768797Methyl 2-amino-5-phenylbenzoate

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a suspension of 5-bromo-2-amino-benzoic acid methyl ester (3.0 g, 13,04 mmol), tetrakis(triphenylphosphine)palladium(0) (0.5 g, 0.44 mmol), toluene (40 ml) and 2 N aqueous sodium carbonate (14.8 ml) was added a solution of phenylboronic acid (2.2 g, 17.73 mmol) in methanol (10 ml) at room temperature. The resulting reaction mixture was heated at reflux temperature for 4 h. cooled and diluted with water (50 ml). The insoluble matter was filtered off and the phases were separated. The aqueous phase was extracted with ethyl acetate (100 ml) and the combined organic phases were washed with water (2×80 ml), diluted aqueous ammoniac (80 ml) and saturated aqueous sodium chloride (80 ml). The organic phase was dried (MgSO4), filtered and evaporated in vacuo affording 3.4 g of crude 4-amino-biphenyl-3-carboxylic acid methyl ester which was purified on silicagel (1 l) using a mixture of ethyl acetate and heptane (1:3) as eluent. Pure fractions were collected and evaporated in vacuo affording 2.7 g (91%) of 4-amino-biphenyl-3-carboxylic acid methyl ester.

Workup

  1. customThe resulting reaction mixture
  2. temperaturewas heated
  3. temperatureat reflux temperature for 4 h.
  4. temperaturecooled
  5. filtrationThe insoluble matter was filtered off
  6. customthe phases were separated
  7. extractionThe aqueous phase was extracted with ethyl acetate (100 ml)
  8. washthe combined organic phases were washed with water (2×80 ml), diluted aqueous ammoniac (80 ml) and saturated aqueous sodium chloride (80 ml)
  9. dry with materialThe organic phase was dried (MgSO4)
  10. filtrationfiltered
  11. customevaporated in vacuo

Sources & evidence

ORD record
ord-aa5aa79bca7f4e42823d21b7af7b36f8
Source dataset
uspto-grants-2001_05
Patent number
US06225329B1

Reaction notes

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