2,2,2-Trichloroethyl chloroformate → Ethyl 4-(3,4-dichlorophenyl)pyrrolidine-3-carboxylate

HRID 1880206Notes

Reaction equation

HRID 1880206 reaction equation
[CH2:1]([O:3][C:4]([CH:6]1[CH:10]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[CH2:9][N:8](CC2C=CC=CC=2)[CH2:7]1)=[O:5])[CH3:2].ClC(OCC(Cl)(Cl)Cl)=O>CC#N>[CH2:1]([O:3][C:4]([CH:6]1[CH:10]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[CH2:9][NH:8][CH2:7]1)=[O:5])[CH3:2]

Participants

4

Reactant 2

HCID 870632,2,2-Trichloroethyl chloroformateHCID 67131665Ethyl 1-benzyl-4-(3,4-dichlorophenyl)pyrrolidine-3-carboxylate

Product 1

HCID 67327572Ethyl 4-(3,4-dichlorophenyl)pyrrolidine-3-carboxylateYield 97.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (3SR,4RS)-1-benzyl-4-(3,4-dichloro-phenyl)-pyrrolidine-3-carboxylic acid ethyl ester (2.50 g, 6.61 mmol) in CH3CN (55 mL) was added 2,2,2-trichloroethyl chloroformate (1.34 mL, 9.91 mmol) and stirring was continued for 4 hours at RT. Volatiles were removed under vacuo, and the residue was dissolved in AcOH (25 mL). Then Zn dust (1.20 g) 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 1.85 g (97%) of the title compound as a light yellow oil. ES-MS m/e: 288.1 (M+H+).

Workup

  1. customVolatiles were removed under vacuo
  2. dissolutionthe residue was dissolved in AcOH (25 mL)
  3. additionThen Zn dust (1.20 g) was added portion wise
  4. filtrationAfter three hours at RT the reaction mixture was filtered on celite
  5. customthe solvent removed under vacuo
  6. extractionfollowed by an extraction with EtOAc/aq
  7. dry with materialThe organic phases were dried on Na2SO4 and column chromatography (SiO2, CH2Cl2/MeOH 9:1)

Sources & evidence

ORD record
ord-9b06aae80d294dae9aafc3afd2698dc5
Source dataset
uspto-grants-2012_11
Patent number
US08318759B2

Reaction notes

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