2,2,2-Trichloroethyl chloroformate → [(3RS,4SR)-4-(3-chloro-phenyl)-pyrrolidin-3-yl]-methyl-(4-trifluoromethyl-benzyl)-amine

HRID 910445Notes

Reaction equation

HRID 910445 reaction equation
C([N:8]1[CH2:12][CH:11]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=2)[CH:10]([N:20]([CH3:32])[CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=2)[CH2:9]1)C1C=CC=CC=1.ClC(OCC(Cl)(Cl)Cl)=O>CC#N>[Cl:19][C:15]1[CH:14]=[C:13]([CH:11]2[CH2:12][NH:8][CH2:9][CH:10]2[N:20]([CH3:32])[CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:29])[F:30])=[CH:24][CH:23]=2)[CH:18]=[CH:17][CH:16]=1

Participants

4

Reactant 2

HCID 870632,2,2-Trichloroethyl chloroformateHCID 67218077[(3RS,4SR)-1-Benzyl-4-(3-chloro-phenyl)-pyrrolidin-3-yl]-methyl-(4-trifluoromethyl-benzyl)-amine

Product 1

HCID 67218391[(3RS,4SR)-4-(3-chloro-phenyl)-pyrrolidin-3-yl]-methyl-(4-trifluoromethyl-benzyl)-amineYield 76%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of [(3RS,4SR)-1-benzyl-4-(3-chloro-phenyl)-pyrrolidin-3-yl]-methyl-(4-trifluoromethyl-benzyl)-amine (500 mg, 1.09 mmol) in CH3CN (7 ml) at RT, was added 2,2,2-trichloroethyl chloroformate (0.22 ml, 1.63 mmol). The reaction mixture was stirred at RT for 3 hours, concentrated under vacuo. The residue was dissolved in AcOH (5 ml) and zinc dust (200 mg) was added portion wise over 1 hours. The solvent was evaporated, the residue diluted in EtOAc and the organic phase was washed with an aqueous solution of NaHCO3. The organic phase was dried over Na2SO4 and concentrated under vacuo. The product was purified by column chromatography (CH2Cl2/MeOH: 9/1) to afford 305 mg (76%) of the tile compound as a colorless oil. ES-MS m/e: 369.2 (M+H+).

Workup

  1. concentrationconcentrated under vacuo
  2. dissolutionThe residue was dissolved in AcOH (5 ml)
  3. additionzinc dust (200 mg) was added portion wise over 1 hours
  4. customThe solvent was evaporated
  5. additionthe residue diluted in EtOAc
  6. washthe organic phase was washed with an aqueous solution of NaHCO3
  7. dry with materialThe organic phase was dried over Na2SO4
  8. concentrationconcentrated under vacuo
  9. customThe product was purified by column chromatography (CH2Cl2/MeOH: 9/1)

Sources & evidence

ORD record
ord-994cc44420dd470c9defe7aa19e4c233
Source dataset
uspto-grants-2011_09
Patent number
US08022099B2

Reaction notes

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