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Potassium Phosphate, Tribasic → 4-[[2-(2,4-difluorophenyl)-5-methyl-2H-1,2,3-triazol-4-yl]methyl]-2-(trifluoromethyl)pyridine

HRID 623711
Notes
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Reaction equation

HRID 623711 reaction equation
Br[CH2:2][C:3]1[C:7]([CH3:8])=[N:6][N:5]([C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=2[F:16])[N:4]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[F:25][C:26]([F:43])([F:42])[C:27]1[CH:32]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH:30]=[CH:29][N:28]=1>O1CCCC1.O.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:16][C:10]1[CH:11]=[C:12]([F:15])[CH:13]=[CH:14][C:9]=1[N:5]1[N:4]=[C:3]([CH2:2][C:31]2[CH:30]=[CH:29][N:28]=[C:27]([C:26]([F:43])([F:42])[F:25])[CH:32]=2)[C:7]([CH3:8])=[N:6]1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 457857082-(Trifluoromethyl)pyridine-4-boronic acid, pinacol esterHCID 901118064-(bromomethyl)-2-(2,4-difluorophenyl)-5-methyl-2H-1,2,3-triazole2×

Product 1

HCID 901104994-[[2-(2,4-difluorophenyl)-5-methyl-2H-1,2,3-triazol-4-yl]methyl]-2-(trifluoromethyl)pyridine

Reagents, catalysts & solvents 3

HCID 178418397
HCID 178418397, compound
Catalyst
HCID 962WaterSolvent
HCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
70 °C

Procedure

To a solution of 4-(bromomethyl)-2-(2,4-difluorophenyl)-5-methyl-2H-1,2,3-triazole (i.e. the product of Step C, 0.30 g, 1.0 mmol) in tetrahydrofuran/water (3:1, 4 mL total), was added tetrakis(triphenylphosphine)palladium(0) (0.058 g, 0.05 mmol), potassium phosphate tribasic (0.43 g, 2.0 mmol) and 2-(trifluoromethyl)pyridine-4-boronic acid pinacol ester (0.31 g, 1.15 mmol). The mixture was heated to 70° C. and stirred for 96 h. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried (MgSO4) and concentrated under reduced pressure. The crude residue was purified by twice by chromatography on silica gel eluting with 0 to 100% ethyl acetate in hexanes, and then was purified by reverse-phase chromatography on C18 silica gel to afford the title compound (0.18 g) as a colorless solid.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic layer was dried (MgSO4)
  3. concentrationconcentrated under reduced pressure
  4. customThe crude residue was purified by twice by chromatography on silica gel eluting with 0 to 100% ethyl acetate in hexanes
  5. customwas purified by reverse-phase chromatography on C18 silica gel

Sources & evidence

ORD record
ord-0f45e3c1ea9d476abd107b5ee03876aa
Source dataset
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09302999B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes