2-Fluoro-5-iodobenzonitrile → 5-[3-(3,5-Dichlorophenyl)-3-(trifluoromethyl)pyrrolidin-1-yl]2-fluorobenzonitrile

HRID 1930524Notes

Reaction equation

HRID 1930524 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:14]([F:17])([F:16])[F:15])[CH2:13][CH2:12][NH:11][CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.[F:18][C:19]1[CH:26]=[CH:25][C:24](I)=[CH:23][C:20]=1[C:21]#[N:22]>C1(C)C=CC=CC=1>[Cl:8][C:6]1[CH:5]=[C:4]([C:9]2([C:14]([F:17])([F:16])[F:15])[CH2:13][CH2:12][N:11]([C:24]3[CH:25]=[CH:26][C:19]([F:18])=[C:20]([CH:23]=3)[C:21]#[N:22])[CH2:10]2)[CH:3]=[C:2]([Cl:1])[CH:7]=1

Participants

4

Reactant 2

HCID 27789282-Fluoro-5-iodobenzonitrileHCID 582188803-(3,5-Dichlorophenyl)-3-(trifluoromethyl)pyrrolidine

Product 1

HCID 582188895-[3-(3,5-Dichlorophenyl)-3-(trifluoromethyl)pyrrolidin-1-yl]2-fluorobenzonitrileYield 63.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidine (0.6 g) and 2-fluoro-5-iodobenzonitrile (0.57 g) was dissolved in toluene, which was then degassed 3 times. To the solution in toluene was added sodium tert-butoxide (0.20 g), Tris(dibenzylidene acetone)dipalladium chloroform complex (0.04 g) and Xantphos (0.07 g) under argon atmosphere, and the mixture was stirred at 80° C. for two hours. The mixture was cooled to room temperature and then diluted with ethyl acetate, which was then washed with water and dried over anhydrous magnesium sulfate. After the drying agent was filtered off, the solvent was distilled away under the reduced pressure, and the residue was then purified by silica gel chromatography to yield 5-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidin-1-yl]-2-fluorobenzonitrile (0.54 g). m.p. 184-186° C.

Workup

  1. customwhich was then degassed 3 times
  2. additionTo the solution in toluene was added sodium tert-butoxide (0.20 g), Tris(dibenzylidene acetone)dipalladium chloroform complex (0.04 g) and Xantphos (0.07 g) under argon atmosphere
  3. temperatureThe mixture was cooled to room temperature
  4. additiondiluted with ethyl acetate, which
  5. washwas then washed with water
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationAfter the drying agent was filtered off
  8. distillationthe solvent was distilled away under the reduced pressure
  9. customthe residue was then purified by silica gel chromatography

Sources & evidence

ORD record
ord-35b896f1465f405881ba9a15f694cda9
Source dataset
uspto-grants-2012_05
Patent number
US08188122B2

Reaction notes

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