Sodium Carbonate → 4-Amino-5-methyl-biphenyl-3-carboxylic acid methyl ester

HRID 651076Notes

Reaction equation

HRID 651076 reaction equation
[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[C:8](Br)[CH:7]=[C:6]([CH3:11])[C:5]=1[NH2:12].[C:14]1(B(O)O)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C([O-])([O-])=O.[Na+].[Na+]>C(COC)OC.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:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:7]=[C:6]([CH3:11])[C:5]=1[NH2:12])=[O:13]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 2763413Methyl 2-amino-5-bromo-3-methylbenzoate

Product 1

HCID 542075304-Amino-5-methyl-biphenyl-3-carboxylic acid methyl esterYield 50%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of 5.0 g (0.021 mol) of 2-amino-5-bromo-3-methyl-benzoic acid methyl ester and 2.8 g (0.023 mol) of phenyl boronic acid in 150 mL of dimethoxyethane was added 20.5 mL of a 2.0M aqueous solution of Na2CO3 and 1.18 g (1.02 mmol) of Pd(PPh3)4. The reaction mixture was evacuated and filled with N2 three times and was then heated to reflux overnight. The reaction was then cooled to room temperature, and poured into ethyl acetate and water. The aqueous layer was extracted three times with ethyl acetate. The combined organics were washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was chromatographed on silica gel using gradient elution (100% hexane to 4/1 hexane/ethyl acetate) to provide 2.5 g (50%) of 4-amino-5-methyl-biphenyl-3-carboxylic acid methyl ester. Electrospray Mass Spec: 241.8 (M+H)+

Workup

  1. customThe reaction mixture was evacuated
  2. additionfilled with N2 three times
  3. temperaturewas then heated
  4. temperatureto reflux overnight
  5. additionpoured into ethyl acetate and water
  6. extractionThe aqueous layer was extracted three times with ethyl acetate
  7. washThe combined organics were washed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo
  10. customThe residue was chromatographed on silica gel using gradient elution (100% hexane to 4/1 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-9e594933d6f9401f905eea31e35e8c79
Source dataset
uspto-grants-2001_08
Patent number
US06277885B1

Reaction notes

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