2,2,2-Trichloroethyl chloroformate → 6-{(SR)-1-[(3RS,4SR)-4-(3,4-Dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-nicotinonitrile

HRID 559281Notes

Reaction equation

HRID 559281 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]([CH:21]([O:23][C:24]2[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][N:25]=2)[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[CH:21]([O:23][C:24]2[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][N:25]=2)[CH3:22])[CH:18]=[CH:17][C:16]=1[Cl:19]

Participants

4

Reactant 2

HCID 870632,2,2-Trichloroethyl chloroformateHCID 669994036-{(SR)-1-[(3RS,4SR)-1-Benzyl-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-nicotinonitrile

Product 1

HCID 669997186-{(SR)-1-[(3RS,4SR)-4-(3,4-Dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-nicotinonitrileYield 60%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 6-{(SR)-1-[(3RS,4SR)-1-benzyl-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-nicotinonitrile 0.75 g (1.70 mmol) dissolved in CH3CN (50 mL) was added 0.56 mL (4.14 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 (30 mL) before a total of 0.45 g 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 an extraction with EtOAc/aq. NaHCO3 (basic pH). The organic phases were dried on Na2SO4 and column chromatography (SiO2, CH2Cl2/MeOH 9:1) yielded 0.36 g (60%) of the title compound as a colorless oil. ES-MS m/e: 362.3 (M+H+).

Workup

  1. customVolatiles were removed under vacuo
  2. dissolutionthe crude was dissolved in AcOH (30 mL) before a total of 0.45 g 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 an 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-0081c44cb2024c40a8d43fd0a9785541
Source dataset
uspto-grants-2011_11
Patent number
US08063075B2

Reaction notes

Loading…