Citric Acid → 3-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyridin-2-ylamine

HRID 1784561Notes

Reaction equation

HRID 1784561 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:9]([F:12])([F:11])[F:10])[C:5]([NH2:8])=[N:6][CH:7]=1.[F:13][C:14]([F:25])([F:24])[C:15]1[CH:20]=[CH:19][C:18](B(O)O)=[CH:17][CH:16]=1.C([O-])([O-])=O.[Na+].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>COCCOC.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:10][C:9]([F:12])([F:11])[C:4]1[C:5]([NH2:8])=[N:6][CH:7]=[C:2]([C:18]2[CH:19]=[CH:20][C:15]([C:14]([F:25])([F:24])[F:13])=[CH:16][CH:17]=2)[CH:3]=1

Participants

7

Reactant 4

HCID 311Citric AcidHCID 10340Sodium CarbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 205253835-Bromo-3-(trifluoromethyl)pyridin-2-amine

Product 1

HCID 866116233-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyridin-2-ylamineYield 87%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of the above 5-bromo-3-trifluoromethyl-pyridin-2-ylamine (9.90 g, 41.1 mmol), commercially available 4-(trifluoromethyl)benzeneboronic acid CAS-No. [128796-39-4] (8.58 g, 45.2 mmol), 1N aqueous Na2CO3-solution (98.6 mL, 98.6 mmol) and Pd(PPh3)4 (475 mg, 1 mol %) in DME (205 mL) was refluxed under argon atmosphere for 1 h. Poured into 5% citric acid, extracted with EtOAc, washed the organic layers with sat. NaHCO3-sol. and brine, dried over Na2SO4. Removal of the solvent in vacuum left a grey solid (13.96 g) which was purified by silica gel flash chromatography with heptane/EtOAc 4:1 to 2:1 to give the title compound as a light yellow solid (10.90 g, 87%). MS (ISN) 305 [(M−H)−]; mp 168° C.

Workup

  1. extractionextracted with EtOAc
  2. washwashed the organic layers with sat. NaHCO3-sol
  3. dry with materialand brine, dried over Na2SO4
  4. customRemoval of the solvent in vacuum
  5. waitleft a grey solid (13.96 g) which
  6. customwas purified by silica gel flash chromatography with heptane/EtOAc 4:1 to 2:1

Sources & evidence

ORD record
ord-0e6c1d8a0de64ca889d7d2dd02613844
Source dataset
uspto-grants-2009_03
Patent number
US07504404B2

Reaction notes

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