Sodium Carbonate → 6-(4-(Trifluoromethyl)phenyl)picolinaldehyde

HRID 1391728Notes

Reaction equation

HRID 1391728 reaction equation
Br[C:2]1[N:7]=[C:6]([CH:8]=[O:9])[CH:5]=[CH:4][CH:3]=1.[F:10][C:11]([F:22])([F:21])[C:12]1[CH:17]=[CH:16][C:15](B(O)O)=[CH:14][CH:13]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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>[F:10][C:11]([F:22])([F:21])[C:12]1[CH:17]=[CH:16][C:15]([C:2]2[N:7]=[C:6]([CH:8]=[O:9])[CH:5]=[CH:4][CH:3]=2)=[CH:14][CH:13]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 27570096-Bromopyridine-2-carbaldehyde

Product 1

HCID 247300896-(4-(Trifluoromethyl)phenyl)picolinaldehydeYield 81.8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of 6-bromo-2-pyridinecarboxaldehyde (512 mg, 2.75 mmol) and 4-(triflouromethyl)benzeneboronic acid (522 mg, 2.75 mmol) in DME (46 mL) was treated a slurry of Na2CO3 (875 mg, 8.26 mmol) in water (23 mL) followed by Pd(PPh3)4 (64 mg, 0.06 mmol). The resulting mixture was then heated to reflux, under nitrogen over 30 minutes and then stirred at this temperature for 17 hours. The mixture was then allowed to cool to rt, was reduced under vacuum and the residue partitioned between EtOAc (50 mL) and water (50 mL) and the layers separated. The aqueous was re-extracted with EtOAc (100 mL) and the combined organic layer washed with brine (100 mL), dried (MgSO4), filtered and reduced to give a yellow solid residue. Purification by SPE (silica) eluting with cyclohexane:EtOAc (gradient 1:0 to 10:1) afforded the title compound as a yellow foam (565 mg).

Workup

  1. temperatureThe resulting mixture was then heated
  2. temperatureto reflux, under nitrogen over 30 minutes
  3. customthe residue partitioned between EtOAc (50 mL) and water (50 mL)
  4. customthe layers separated
  5. extractionThe aqueous was re-extracted with EtOAc (100 mL)
  6. washthe combined organic layer washed with brine (100 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customto give a yellow solid residue
  10. customPurification by SPE (silica)
  11. washeluting with cyclohexane

Sources & evidence

ORD record
ord-0052238f1e8f41a9829fce10c7234ce0
Source dataset
uspto-grants-2008_03
Patent number
US07338960B2

Reaction notes

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