Hydrochloric Acid → 2-Bromo-4-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)-pyrrolidin-1-yl]aniline

HRID 1930522Notes

Reaction equation

HRID 1930522 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([N:11]2[CH2:15][CH2:14][C:13]([C:20]3[CH:25]=[C:24]([Cl:26])[CH:23]=[C:22]([Cl:27])[CH:21]=3)([C:16]([F:19])([F:18])[F:17])[CH2:12]2)[CH:5]=[CH:6][C:7]=1[N+:8]([O-])=O.O1CCOCC1.Cl.C(=O)([O-])O.[Na+]>O.C(OCC)(=O)C.C(O)C>[Br:1][C:2]1[CH:3]=[C:4]([N:11]2[CH2:15][CH2:14][C:13]([C:20]3[CH:21]=[C:22]([Cl:27])[CH:23]=[C:24]([Cl:26])[CH:25]=3)([C:16]([F:17])([F:18])[F:19])[CH2:12]2)[CH:5]=[CH:6][C:7]=1[NH2:8]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 866523891-(3-Bromo-4-nitrophenyl)-3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidine

Product 1

HCID 582188902-Bromo-4-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)-pyrrolidin-1-yl]anilineYield 70.7%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the solution of 1-(3-bromo-4-nitrophenyl)-3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidine (1.10 g) in the mixed solvent of 1,4-dioxane and ethanol was added stannous chloride dihydrate (2.05 g) and a small amount of concentrated hydrochloric acid, and the mixture was then stirred 4 hours at 90° C. The mixture was cooled to room temperature and then poured into the mixed solution of ethyl acetate and water, which was then neutralized with sodium hydrogen carbonate with vigorous stirring. After filtration of precipitate through Celite, the organic layer was separated and the aqueous layer was extracted with ethyl acetate. The organic layer was combined, which was then washed with brine 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 2-bromo-4-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)-pyrrolidin-1-yl]aniline (0.73 g). 1H-NMR (CDCl3) δ: 2.44-2.54 (1H, m), 2.75-2.83 (1H, m), 3.32-3.50 (2H, m), 3.56-3.76 (3H, m), 3.92 (1H, d), 6.46 (1H, dd), 6.70-6.78 (2H, m), 7.29 (2H, br s), 7.37 (1H, t).

Workup

  1. filtrationAfter filtration of precipitate through Celite
  2. customthe organic layer was separated
  3. extractionthe aqueous layer was extracted with ethyl acetate
  4. washwhich was then washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationAfter the drying agent was filtered off
  7. distillationthe solvent was distilled away under the reduced pressure
  8. customthe residue was then purified by silica gel chromatography

Sources & evidence

ORD record
ord-ed74d3efc60f4e8b8fc67ee2655637a3
Source dataset
uspto-grants-2012_05
Patent number
US08188122B2

Reaction notes

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