2,2,2-Trichloroethyl chloroformate → 1-[(3SR,4RS)-4-(3,4-Dichloro-phenyl)-pyrrolidin-3-yl]-ethanone

HRID 906908Notes

Reaction equation

HRID 906908 reaction equation
C([N:8]1[CH2:12][CH:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([Cl:20])[CH:14]=2)[CH:10]([C:21](=[O:23])[CH3:22])[CH2:9]1)C1C=CC=CC=1.ClC(OCC(Cl)(Cl)Cl)=O>CC#N>[Cl:20][C:15]1[CH:14]=[C:13]([CH:11]2[CH2:12][NH:8][CH2:9][CH:10]2[C:21](=[O:23])[CH3:22])[CH:18]=[CH:17][C:16]=1[Cl:19]

Participants

4

Reactant 2

HCID 870632,2,2-Trichloroethyl chloroformateHCID 669997301-[(3RS,4SR)-1-Benzyl-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethanone

Product 1

HCID 671317481-[(3SR,4RS)-4-(3,4-Dichloro-phenyl)-pyrrolidin-3-yl]-ethanoneYield 63.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 1-[(3SR,4RS)-1-benzyl-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethanone (IX-1) 4.00 g (9.20 mmol) dissolved in CH3CN (50 mL) was added 2.48 mL (18.40 mmol) of 2,2,2-trichloroethyl chloroformate and stirring was continued for 3 hours at RT. Volatiles were removed under vacuo, and the crude residue was dissolved in AcOH (30 mL) before a total of 1.5 g of Zn dust was added portionwise. 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 to 8:2) yielded 1.50 g (63%) of the title compound as a colorless oil. ES-MS m/e: 258.0 (M+H+).

Workup

  1. customVolatiles were removed under vacuo
  2. dissolutionthe crude residue was dissolved in AcOH (30 mL) before a total of 1.5 g of Zn dust
  3. additionwas added portionwise
  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 to 8:2)

Sources & evidence

ORD record
ord-c28b66eaad03466b890852cfb45f7be4
Source dataset
uspto-grants-2011_09
Patent number
US08012998B2

Reaction notes

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