Tetrafluoroboric acid → 4-Chloro-5-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-2-methoxy-benzoic acid

HRID 448938Notes

Reaction equation

HRID 448938 reaction equation
[C:1]([C:4]1[C:5]([O:14][CH3:15])=[CH:6][C:7]([Cl:13])=[C:8](B(O)O)[CH:9]=1)([OH:3])=[O:2].Br[C:17]1[C:22]([C:23]#[N:24])=[CH:21][C:20]([C:25]([F:28])([F:27])[F:26])=[N:19][CH:18]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].P(C(C)(C)C)(C(C)(C)C)C(C)(C)C.[H+].[B-](F)(F)(F)F>C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:13][C:7]1[C:8]([C:17]2[CH:18]=[N:19][C:20]([C:25]([F:27])([F:28])[F:26])=[CH:21][C:22]=2[C:23]#[N:24])=[CH:9][C:4]([C:1]([OH:3])=[O:2])=[C:5]([O:14][CH3:15])[CH:6]=1

Participants

8

Reactant 5

HCID 28118Tetrafluoroboric acidHCID 62657Potassium Phosphate, TribasicHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 441195965-Borono-4-chloro-2-methoxybenzoic acidHCID 569733155-Bromo-2-(trifluoromethyl)isonicotinonitrile

Product 1

HCID 686021944-Chloro-5-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-2-methoxy-benzoic acidYield 44.4%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

N2 was bubbled through a solution of THF (8 mL) and water (2 mL) containing 5-carboxy-2-chloro-4-methoxy-phenylboronic acid (460.8 mg, 2.0 mmol) and 5-bromo-2-trifluoromethyl-isonicotinonitrile 1-1 (478 mg, 1.9 mmol) for 10 minutes. K3PO4 (1.2 g, 5.7 mmol), t-Bu3P.HBF4 (82.7 mg, 0.28 mmol), and Pd2 dba3 (91.0 mg, 0.1 mmol) were added under N2 atmosphere. The mixture was sealed, stirred at rt for 3 hrs, and diluted with ethyl acetate. The organic layer was separated, washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified via silica gel flash column chromatography eluting with 10% MeOH in dichloromethane to give 4-chloro-5-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-2-methoxy-benzoic acid (301 mg).

Workup

  1. customN2 was bubbled through a solution of THF (8 mL) and water (2 mL)
  2. customThe mixture was sealed
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified via silica gel flash column chromatography
  9. washeluting with 10% MeOH in dichloromethane

Sources & evidence

ORD record
ord-fb1c6091c6264ab1a3a1914316f60961
Source dataset
uspto-grants-2013_07
Patent number
US08481738B2

Reaction notes

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