2,2,2-Trichloroethyl chloroformate → 5-Chloro-2-{(RS)-1-[(3SR,4RS)-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-pyridine

HRID 559280Notes

Reaction equation

HRID 559280 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:29]=[CH:28][C:27]([Cl:30])=[CH:26][N:25]=2)[CH3:22])[CH2:9]1)C1C=CC=CC=1.ClC(OCC(Cl)(Cl)Cl)=O>CC#N>[Cl:30][C:27]1[CH:28]=[CH:29][C:24]([O:23][CH:21]([CH:10]2[CH:11]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([Cl:20])[CH:14]=3)[CH2:12][NH:8][CH2:9]2)[CH3:22])=[N:25][CH:26]=1

Participants

4

Reactant 2

HCID 870632,2,2-Trichloroethyl chloroformateHCID 669995232-{(RS)-1-[(3SR,4RS)-1-Benzyl-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-5-chloro-pyridine

Product 1

HCID 669991845-Chloro-2-{(RS)-1-[(3SR,4RS)-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-pyridineYield 54%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-{(SR)-1-[(3RS,4SR)-1-benzyl-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-5-chloro-pyridine (1.71 g (3.71 mmol) dissolved in CH3CN (50 mL) was added 0.75 mL (5.57 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 1.0 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 0.74 g (54%) of the title compound as a colorless oil. ES-MS m/e: 373.1 (M+H+).

Workup

  1. customVolatiles were removed under vacuo
  2. dissolutionthe crude was dissolved in AcOH (30 mL) before a total of 1.0 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-a493fbd8272547fbbe5f1617a3e07b3d
Source dataset
uspto-grants-2011_11
Patent number
US08063075B2

Reaction notes

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