Sodium Hydroxide → 2-(5-Fluoro-2-{[4'-(trifluoromethyl)-1,1'-biphenyl-4-yl]methoxy}phenyl)ethylamine

HRID 1921898Notes

Reaction equation

HRID 1921898 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=3)=[CH:15][CH:14]=2)=[C:6]([CH2:8][C:9]#[N:10])[CH:7]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl-].[Cl-].[Cl-].[Al+3].[OH-].[Na+]>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:26])([F:27])[F:28])=[CH:21][CH:20]=3)=[CH:15][CH:14]=2)=[C:6]([CH2:8][CH2:9][NH2:10])[CH:7]=1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 6451240Aluminum(III) ChlorideHCID 21226445Aluminium lithium hydrideHCID 579719252-(5-Fluoro-2-((4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)methoxy)phenyl)acetonitrile

Product 1

HCID 579719282-(5-Fluoro-2-{[4'-(trifluoromethyl)-1,1'-biphenyl-4-yl]methoxy}phenyl)ethylamine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

140.97 g (0.366 mol) of (5-fluoro-2-{[4′-(trifluoromethyl)-1,1′-biphenyl-4-yl]methoxy}phenyl)-acetonitrile are dissolved in 701 ml of anhydrous THF under argon and, after cooling to 0° C., 361.6 ml (0.362 mol) of a 1 M solution of lithium aluminum hydride in THF are added. Then 73.2 g (0.55 mol) of aluminum trichloride in 701 ml of THF are slowly added dropwise to the reaction solution. The reaction mixture is stirred at room temperature for 3.5 h. After reaction is complete, the solution is cooled to 0° C. and aqueous sodium hydroxide solution is slowly added. The aqueous phase is extracted three times with ethyl acetate, and the combined organic phases are dried over sodium sulfate, filtered and concentrated to dryness in vacuo. The crude product is purified by chromatography on 10 kg of silica gel (mobile phase: dichloromethane/methanol 6:4). 90.28 g (61% of theory) of the title compound are obtained.

Workup

  1. customAfter reaction
  2. temperaturethe solution is cooled to 0° C.
  3. extractionThe aqueous phase is extracted three times with ethyl acetate
  4. dry with materialthe combined organic phases are dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness in vacuo
  7. customThe crude product is purified by chromatography on 10 kg of silica gel (mobile phase: dichloromethane/methanol 6:4)

Sources & evidence

ORD record
ord-06d38c85e9e6447b9907e7a7bc636a80
Source dataset
uspto-grants-2012_05
Patent number
US08173704B2

Reaction notes

Loading…