2,2,2-Trichloroethyl chloroformate → (3RS,4SR)-3-(3,4-Dichloro-phenyl)-4-[(RS)-1-(4-trifluoromethyl-phenoxy)-ethyl]-pyrrolidine

HRID 906869Notes

Reaction equation

HRID 906869 reaction equation
C([N:8]1[CH2:12][CH:11]([CH:13]([O:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=2)[CH3:14])[CH:10]([C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[C:28]([Cl:33])[CH:27]=2)[CH2:9]1)C1C=CC=CC=1.ClC(OCC(Cl)(Cl)Cl)=O>CC#N>[Cl:33][C:28]1[CH:27]=[C:26]([CH:10]2[CH:11]([CH:13]([O:15][C:16]3[CH:17]=[CH:18][C:19]([C:22]([F:24])([F:25])[F:23])=[CH:20][CH:21]=3)[CH3:14])[CH2:12][NH:8][CH2:9]2)[CH:31]=[CH:30][C:29]=1[Cl:32]

Participants

4

Reactant 2

HCID 870632,2,2-Trichloroethyl chloroformateHCID 67131473(3RS,4SR)-1-Benzyl-3-(3,4-dichloro-phenyl)-4-[(RS)-1-(4-trifluoromethyl-phenoxy)-ethyl]-pyrrolidine

Product 1

HCID 67131736(3RS,4SR)-3-(3,4-Dichloro-phenyl)-4-[(RS)-1-(4-trifluoromethyl-phenoxy)-ethyl]-pyrrolidineYield 67%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (3RS,4SR)-1-benzyl-3-(3,4-dichloro-phenyl)-4-[(RS)-1-(4-trifluoromethyl-phenoxy)-ethyl]-pyrrolidine (XI-B-1) 0.99 g (2.00 mmol) dissolved in CH3CN (25 mL) was added 0.40 mL (3.00 mmol) of 2,2,2-trichloroethyl chloroformate and stirring was continued for 4 hours at RT. Volatiles were removed under vacuo, and the crude was dissolved in AcOH (20 mL) before a total of 800 mg of Zn dust was added portion wise. After three hours at RT, the reaction mixture was filtered on celite, the solvent removed under vacuo, followed by extraction with EtOAc/aq. NaHCO3 (basic pH). The organic phases were dried on Na2SO4 and column chromatography (SiO2, CH2Cl2/MeOH 9:1) yielded 0.54 g (67%) of the title compound as a colorless oil. ES-MS m/e: 404.2 (M+H+).

Workup

  1. customVolatiles were removed under vacuo
  2. dissolutionthe crude was dissolved in AcOH (20 mL) before a total of 800 mg of Zn dust
  3. additionwas added portion wise
  4. waitAfter three hours at RT
  5. filtrationthe reaction mixture was filtered on celite
  6. customthe solvent removed under vacuo
  7. extractionfollowed by extraction with EtOAc/aq
  8. dry with materialThe organic phases were dried on Na2SO4 and column chromatography (SiO2, CH2Cl2/MeOH 9:1)

Sources & evidence

ORD record
ord-ac6c41a0054e4beb83b6567fd5f520c6
Source dataset
uspto-grants-2011_09
Patent number
US08012998B2

Reaction notes

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