4-(Trifluoromethyl)aniline → (2R,5S)-2,5-bis(4-bromophenyl)-1-(4-(trifluoromethyl)phenyl)pyrrolidine

HRID 1470962Notes

Reaction equation

HRID 1470962 reaction equation
CS(O[CH:6]([C:22]1[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][CH:23]=1)[CH2:7][CH2:8][CH:9](OS(C)(=O)=O)[C:10]1[CH:15]=[CH:14][C:13]([Br:16])=[CH:12][CH:11]=1)(=O)=O.[F:29][C:30]([F:39])([F:38])[C:31]1[CH:37]=[CH:36][C:34]([NH2:35])=[CH:33][CH:32]=1>CN(C=O)C>[Br:16][C:13]1[CH:14]=[CH:15][C:10]([C@H:9]2[CH2:8][CH2:7][C@@H:6]([C:22]3[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][CH:23]=3)[N:35]2[C:34]2[CH:36]=[CH:37][C:31]([C:30]([F:29])([F:38])[F:39])=[CH:32][CH:33]=2)=[CH:11][CH:12]=1

Participants

4

Reactant 2

HCID 99644-(Trifluoromethyl)anilineHCID 582265311,4-Bis(4-bromophenyl)butane-1,4-diyl dimethanesulfonate

Product 1

HCID 67236564(2R,5S)-2,5-bis(4-bromophenyl)-1-(4-(trifluoromethyl)phenyl)pyrrolidineYield 10%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

The product from Example 42B (11.13 g, 20.0 mmol) and 4-(trifluoromethyl)aniline (Aldrich, 32.2 g, 200 mmol) were combined in DMF (50 mL), stirred at 50° C. under nitrogen for 16 hours, cooled and concentrated. The residue was diluted with ethyl acetate, treated with 1M HCl, stirred for 10 minutes and filtered to remove solids. The organic layer of the filtrate was washed with brine, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography (silica gel, 0 to 1% ethyl acetate/hexane) to give the title compound (1.0 g, 10%) as the second eluting stereoisomer. MS (ESI+) m/z 526 (M+H)+.

Workup

  1. temperaturecooled
  2. concentrationconcentrated
  3. additionThe residue was diluted with ethyl acetate
  4. additiontreated with 1M HCl
  5. stirringstirred for 10 minutes
  6. filtrationfiltered
  7. customto remove solids
  8. washThe organic layer of the filtrate was washed with brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified by flash chromatography (silica gel, 0 to 1% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-b0cb413cdcca408bb67d9ae30fd39c6f
Source dataset
uspto-grants-2015_04
Patent number
US09006387B2

Reaction notes

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