Potassium Carbonate → Methyl 2-cyano-4-biphenylcarboxylate

HRID 2189749Notes

Reaction equation

HRID 2189749 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1OS(C(F)(F)F)(=O)=O)[C:6]([O:8][CH3:9])=[O:7])#[N:2].[C:21]1(B(O)O)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(OCC)(=O)C>[C:1]([C:3]1[CH:4]=[C:5]([C:6]([O:8][CH3:9])=[O:7])[CH:10]=[CH:11][C:12]=1[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)#[N:2]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 53821226Methyl 3-Cyano-4-(trifluoromethylsulfonyloxy)benzoate

Product 1

HCID 53846446Methyl 2-cyano-4-biphenylcarboxylateYield 81.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

The following reaction was split into two batches with half the amounts: methyl 3-cyano-4-{[(trifluoromethyl)sulfonyl]oxy}benzoate (D19) (1.5 g, 4.85 mmol), phenylboronic acid (1.183 g, 9.70 mmol), potassium carbonate (2.011 g, 14.55 mmol) and palladium tetrakistriphenylphosphine(0) (0.561 g, 0.485 mmol) were dissolved in DMF (24 ml) and the mixture heated in the microwave for 30 min at 150° C. The two reactions were combined and diluted with ethyl acetate (50 mL) and the mixture filtered through kieselguhr to remove palladium residues. The filtrate was concentrated in vacuo to reduce the amount of DMF and then the residue partitioned between saturated aqueous sodium bicarbonate (50 mL) and ethyl acetate (50 mL). The organic phase was washed with further sodium bicarbonate (50 mL) and then water (50 mL) before it was dried (MgSO4), filtered and the solvent removed in vacuo. The brown solid was purified by silica chromatography, eluting with 0-25% EtOAc in iso-hexane over 35 minutes to give the title compound as a white solid (935 mg, 3.94 mmol). δH (d6-DMSO, 400 MHz): 8.42 (1H, d), 8.29 (1H, dd), 7.81 (1H, d), 7.65 (2H, m), 7.60-7.50 (3H, m), 3.92 (3H, s).

Workup

  1. customThe following reaction
  2. customwas split into two batches with half the amounts
  3. filtrationthe mixture filtered through kieselguhr
  4. customto remove palladium residues
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue partitioned between saturated aqueous sodium bicarbonate (50 mL) and ethyl acetate (50 mL)
  7. washThe organic phase was washed with further sodium bicarbonate (50 mL)
  8. dry with materialwater (50 mL) before it was dried (MgSO4)
  9. filtrationfiltered
  10. customthe solvent removed in vacuo
  11. customThe brown solid was purified by silica chromatography
  12. washeluting with 0-25% EtOAc in iso-hexane over 35 minutes

Sources & evidence

ORD record
ord-c7f76222f4f542ca911ac6a9d87ec759
Source dataset
uspto-grants-2012_12
Patent number
US08324254B2

Reaction notes

Loading…