Sodium Carbonate → 6-(3-Fluoro-4-(trifluoromethoxy)phenyl)-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine

HRID 2205732Notes

Reaction equation

HRID 2205732 reaction equation
[F:1][C:2]([F:16])([F:15])[C:3]1[N:7]2[CH:8]=[C:9](B(O)O)[CH:10]=[CH:11][C:6]2=[N:5][N:4]=1.Br[C:18]1[CH:23]=[CH:22][C:21]([O:24][C:25]([F:28])([F:27])[F:26])=[C:20]([F:29])[CH:19]=1.C([O-])([O-])=O.[Na+].[Na+]>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.CN(C=O)C>[F:29][C:20]1[CH:19]=[C:18]([C:9]2[CH:10]=[CH:11][C:6]3[N:7]([C:3]([C:2]([F:16])([F:15])[F:1])=[N:4][N:5]=3)[CH:8]=2)[CH:23]=[CH:22][C:21]=1[O:24][C:25]([F:26])([F:27])[F:28]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27822174-Bromo-2-fluoro-1-(trifluoromethoxy)benzeneHCID 581189153-(Trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-ylboronic acid

Product 1

HCID 866502296-(3-Fluoro-4-(trifluoromethoxy)phenyl)-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-ylboronic acid (56.2 mg, 0.217 mmol), 4-bromo-2-fluoro-1-(trifluoromethoxy)benzene (50.0 mg, 0.217 mmol, 1.0 equiv.) and Pd(PPh3)4 (12.6 mg, 0.0109 mmol, 0.05 equiv.) was placed in a 50 mL round bottomed flask under a nitrogen atmosphere. To the flask were added 2M-Na2CO3 (1.0 mL, 2.0 mmol) and DMF (4 mL) subsequently at ambient temperature. The mixture was heated at 110° C. for 1 hours. The mixture was filtered through Celite (3 g) and the Celite was washed with EtOAc (70 mL). The organic layer was washed with brine (30 mL) and dried with Na2SO4. The solvent was removed under a reduced pressure. Obtained crude mixture was purified by a column chromatography (SiO2=25 g, EtOAc/hexane=1:3 to 1:1, Rf=0.3 with EtOAc/hexane=1:1) to give 6-(3-fluoro-4-(trifluoromethoxy)phenyl)-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine as colorless crystals

Workup

  1. filtrationThe mixture was filtered through Celite (3 g)
  2. washthe Celite was washed with EtOAc (70 mL)
  3. washThe organic layer was washed with brine (30 mL)
  4. dry with materialdried with Na2SO4
  5. customThe solvent was removed under a reduced pressure
  6. customObtained crude mixture
  7. customwas purified by a column chromatography (SiO2=25 g, EtOAc/hexane=1:3 to 1:1, Rf=0.3 with EtOAc/hexane=1:1)

Sources & evidence

ORD record
ord-f00a47c2c58a4e8b92b7d7a53341e60d
Source dataset
uspto-grants-2016_06
Patent number
US09371329B2

Reaction notes

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