Triethylamine → ((E)-2-phenyl-1-trifluoromethylvinyl)amine

HRID 244403Notes

Reaction equation

HRID 244403 reaction equation
FC1C=CC([N:8]2C3C(=CC(N)=CC=3)C=N2)=CC=1.[F:18][C:19]([F:30])([F:29])[C:20](=O)[CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(N(CC)CC)C.[BH4-].[Na+].[OH-].[Na+]>ClCCl.Cl[Ti](Cl)(Cl)Cl.CO>[C:22]1(/[CH:21]=[C:20](/[NH2:8])\[C:19]([F:30])([F:29])[F:18])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 2229581,1,1-Trifluoro-3-phenyl-2-propanoneHCID 4311764Sodium borohydrideHCID 592357271-(4-Fluorophenyl)-1h-indazol-5-amine

Product 1

HCID 131731205((E)-2-phenyl-1-trifluoromethylvinyl)amine

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 100 mg (0.44 mmol) of 1-(4-fluorophenyl)-1H-indazol-5-ylamine in 5 mL of dichloromethane was added 60 μL (1.04 mmol) of 1,1,1-trifluoro-3-phenylpropan-2-one, 70 μL (0.97 mmol) of triethylamine followed by 130 μL (1.02 mmol) of TiCl4. The mixture was stirred for 20 hours and then MeOH was added followed by 200 mg (5.29 mmol) of sodium borohydride. After 1 hour, the mixture was diluted 50 mL of 1N aqueous NaOH and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated in vacuo. The crude material was purified by Combiflash chromatography using a EtOAc-hexanes (0-70% gradient) to provide 70 mg (37%) of [144-fluorophenyl)-1H-indazol-5-yl]-((E)-2-phenyl-1-trifluoromethylvinyl)amine as a yellow solid.

Workup

  1. waitAfter 1 hour
  2. extractionextracted with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by Combiflash chromatography

Sources & evidence

ORD record
ord-09aaf42162be40c78eb3df57b20ac493
Source dataset
uspto-grants-2014_02
Patent number
US08658637B2

Reaction notes

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