Potassium Fluoride → 4'-Cyano-6-methyl-biphenyl-3-carboxylic acid methyl ester

HRID 1890247Notes

Reaction equation

HRID 1890247 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6](I)[CH:5]=1.[C:13]([C:15]1[CH:20]=[CH:19][C:18](B(O)O)=[CH:17][CH:16]=1)#[N:14].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.[F-].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[CH3:1][O:2][C:3]([C:4]1[CH:5]=[C:6]([C:18]2[CH:19]=[CH:20][C:15]([C:13]#[N:14])=[CH:16][CH:17]=2)[C:7]([CH3:10])=[CH:8][CH:9]=1)=[O:12]

Participants

7

Reactant 4

HCID 522689Potassium FluorideHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 27343264-Cyanophenylboronic acidHCID 13614033Methyl 3-iodo-4-methylbenzoate

Product 1

HCID 594367074'-Cyano-6-methyl-biphenyl-3-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

To a round-bottom flask containing 3-iodo-4-methyl-benzoic acid methyl ester (1.38 g, 5.00 mmol), 4-cyanophenylboronic acid (1.10 g, 7.48 mmol), palladium acetate (168 mg, 0.748 mmol), 2-(dicyclohexylphosphino)biphenyl (0.526 g, 1.50 mmol) and potassium fluoride (0.870 g, 15.0 mmol) is added anhydrous 1,4-dioxane (15 ml). The flask is purged with argon and sealed. The mixture is stirred at 130° C. for 18 hours, cooled to ambient temperature and then water (20 ml) and ethyl acetate (20 ml) are added. Solid is removed under vacuum filtration. The filtrate is extracted with EtOAc (20 ml×2). The organic layers are combined, washed with aqueous HCl (5%, 20 ml) and saturated NaHCO3 (20 ml). It is dried over MgSO4, and concentrated. The residue is purified by silica gel column chromatography (EtOAc/Hexane, gradient) to give 4′-cyano-6-methyl-biphenyl-3-carboxylic acid methyl ester 2; LC-MS m/z: 252.1 (M+1).

Workup

  1. customThe flask is purged with argon
  2. customsealed
  3. temperaturecooled to ambient temperature
  4. additionwater (20 ml) and ethyl acetate (20 ml) are added
  5. customSolid is removed under vacuum filtration
  6. extractionThe filtrate is extracted with EtOAc (20 ml×2)
  7. washwashed with aqueous HCl (5%, 20 ml) and saturated NaHCO3 (20 ml)
  8. dry with materialIt is dried over MgSO4
  9. concentrationconcentrated
  10. customThe residue is purified by silica gel column chromatography (EtOAc/Hexane, gradient)

Sources & evidence

ORD record
ord-9fb35076daf64d09989fbff917a15964
Source dataset
uspto-grants-2013_08
Patent number
US08507471B2

Reaction notes

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