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

HRID 2066985Notes

Reaction equation

HRID 2066985 reaction equation
C([N:8]1[CH2:12][CH:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([F:20])[CH:14]=2)[CH:10]([N:21]([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[C:26]([F:34])[CH:25]=2)[CH3:22])[CH2:9]1)C1C=CC=CC=1.ClC(OCC(Cl)(Cl)Cl)=O>CC#N>[Cl:19][C:16]1[CH:17]=[CH:18][C:13]([CH:11]2[CH2:12][NH:8][CH2:9][CH:10]2[N:21]([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:31])[F:32])=[C:26]([F:34])[CH:25]=2)[CH3:22])=[CH:14][C:15]=1[F:20]

Participants

4

Reactant 2

HCID 870632,2,2-Trichloroethyl chloroformateHCID 86641316[(3RS,4SR)-1-Benzyl-4-(4-chloro-3-fluoro-phenyl)-pyrrolidin-3-yl]-(3-fluoro-4-trifluoromethyl-benzyl)-methyl-amine

Product 1

HCID 72253482[(3RS,4SR)-4-(4-Chloro-3-fluoro-phenyl)-pyrrolidin-3-yl]-(3-fluoro-4-trifluoromethyl-benzyl)-methyl-amineYield 68.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of [(3RS,4SR)-1-benzyl-4-(4-chloro-3-fluoro-phenyl)-pyrrolidin-3-yl]-(3-fluoro-4-trifluoromethyl-benzyl)-methyl-amine (145 mg, 0.29 mmol) in CH3CN (2 ml) at RT, was added 2,2,2-trichloroethyl chloroformate (0.06 ml, 0.44 mmol). The reaction mixture was stirred at RT for 3 hours, concentrated under vacuo. The residue was dissolved in AcOH (3 ml) and zinc dust (60 mg) was added portion wise over 3 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, concentrated under vacuo to afford 80 mg (67%) of the tile compound as a colorless oil. ES-MS m/e: 405.3 (M+H+).

Workup

  1. concentrationconcentrated under vacuo
  2. dissolutionThe residue was dissolved in AcOH (3 ml)
  3. additionzinc dust (60 mg) was added portion wise over 3 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

Sources & evidence

ORD record
ord-31727d49ef6c43a5bba7cd9665a137ae
Source dataset
uspto-grants-2012_10
Patent number
US08293770B2

Reaction notes

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