Potassium Carbonate → 3-(Chloro-difluoro-methyl)-6-(4-trifluoromethoxy-phenyl)-[1,2,4]triazolo[4,3-a]pyridine

HRID 406440Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([Cl:14])([F:13])[F:12])=[N:9][N:10]=2)[CH:7]=1.[F:15][C:16]([F:28])([F:27])[O:17][C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:14][C:11]([F:13])([F:12])[C:8]1[N:6]2[CH:7]=[C:2]([C:21]3[CH:20]=[CH:19][C:18]([O:17][C:16]([F:15])([F:27])[F:28])=[CH:23][CH:22]=3)[CH:3]=[CH:4][C:5]2=[N:10][N:9]=1

Participants

Conditions

Temperature: 70 °C

Procedure

6-Bromo-3-(chloro-difluoro-methyl)-[1,2,4]triazolo[4,3-a]pyridine (2.76 g, 9.8 mmol), 4-trifluoromethoxyphenyl boronic acid (2.5 g, 12.1 mmol), dppfPdCl2 (1,1′-bis(diphenylphosphino)ferrocene palladium dichloride)(350 mg, 0.5 mmol), and potassium carbonate (2.76 g, 20 mmol) were suspended in degassed toluene (20 mL), degassed isopropanol (10 mL) and degassed water (10 mL) under an atmosphere of nitrogen. The reaction mixture was heated at 70° C. for 1 hour before being cooled to room temperature. The aqueous phase was discarded and the organic phase was concentrated and purified by flash chromatography (rf=0.5 in 1:1 hexanes/ethyl acetate) to give 3-(chloro-difluoro-methyl)-6-(4-trifluoromethoxy-phenyl)-[1,2,4]triazolo[4,3-a]pyridine as a pale orange powder.

Workup

customdegassed isopropanol (10 mL)
customdegassed water (10 mL) under an atmosphere of nitrogen
temperaturebefore being cooled to room temperature
concentrationthe organic phase was concentrated
custompurified by flash chromatography (rf=0.5 in 1:1 hexanes/ethyl acetate)

Sources & evidence

ORD record: ord-9be0f3983da2461e98dd0105f08f7555
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754103B2

Reaction notes

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