Sodium Carbonate → 1-{6-[4-(Trifluoromethyl)phenyl]-2-pyridinyl}-1-pentanone

HRID 1391726

Reaction equation

HRID 1391726 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8](=[O:13])[CH2:9][CH2:10][CH2:11][CH3:12])[CH:5]=[CH:4][CH:3]=1.[F:14][C:15]([F:26])([F:25])[C:16]1[CH:21]=[CH:20][C:19](B(O)O)=[CH:18][CH:17]=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:14][C:15]([F:26])([F:25])[C:16]1[CH:21]=[CH:20][C:19]([C:2]2[N:7]=[C:6]([C:8](=[O:13])[CH2:9][CH2:10][CH2:11][CH3:12])[CH:5]=[CH:4][CH:3]=2)=[CH:18][CH:17]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 586298071-(6-Bromopyridin-2-yl)pentan-1-one

Product 1

HCID 586299011-{6-[4-(Trifluoromethyl)phenyl]-2-pyridinyl}-1-pentanoneYield 94.8%

Reagents, catalysts & solvents 3

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

Procedure

A solution of 1-(6-bromo-2-pyridinyl)-1-pentanone (2.51 g, 10.37 mmol) in DME (13 mL) was treated with 4-(triflouromethyl)benzeneboronic acid (2.36 g, 12.43 mmol), Pd(PPh3)4 (1.19 g, 1.03 mmol) and then a slurry of Na2CO3 (3.29 g, 31.04 mmol) in water (13 mL). The resulting mixture was then heated to reflux over 30 minutes and then stirred at this temperature for 17 hours. The mixture was then allowed to cool to rt and was reduced and the residue partitioned between EtOAc (200 mL) and water (200 mL). The aqueous was re-extracted with EtOAc (100 mL) and the combined organic layer washed with saturated aqueous NaHCO3 (250 mL), brine (250 mL), dried (MgSO4), filtered and reduced to give a brown orange solid residue. Purification by Biotage™ chromatography (silica) eluting with cyclohexane:EtOAc (gradient 1:0 to 10:1) afforded the title compound as a white solid (3.02 g).

Workup

  1. temperatureThe resulting mixture was then heated
  2. temperatureto reflux over 30 minutes
  3. customthe residue partitioned between EtOAc (200 mL) and water (200 mL)
  4. extractionThe aqueous was re-extracted with EtOAc (100 mL)
  5. washthe combined organic layer washed with saturated aqueous NaHCO3 (250 mL), brine (250 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customto give a brown orange solid residue
  9. customPurification by Biotage™ chromatography (silica)
  10. washeluting with cyclohexane

Sources & evidence

ORD record
ord-2323f8da141c47a6b4b89f7651ed89ba
Source dataset
uspto-grants-2008_03
Patent number
US07338960B2

Linked notes

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