Potassium Carbonate → 2-(4-Fluoro-phenyl)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

HRID 1644817Notes

Reaction equation

HRID 1644817 reaction equation
[CH3:1][O:2][C:3](=[O:24])[CH:4]([N:12]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:14][CH2:15]Cl)[C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1>[CH3:1][O:2][C:3]([C:4]1([C:5]2[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=2)[CH2:15][CH2:14][CH2:13][N:12]1[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[O:24]

Participants

5

Reactant 2

HCID 11430Potassium Carbonate2×HCID 66775166[Tert-butoxycarbonyl-(3-chloro-propyl)-amino]-(4-fluoro-phenyl)-acetic acid methyl ester

Product 1

HCID 667735252-(4-Fluoro-phenyl)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

Reagents, catalysts & solvents 2

HCID 66133Benzyl triethylammonium chlorideCatalyst2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of [tert-butoxycarbonyl-(3-chloro-propyl)-amino]-(4-fluoro-phenyl)-acetic acid methyl ester (10.91 g) in acetonitrile (60 mL) was added benzyltriethylammoniumchloride (3.32 g) (see also Chemistry of Heterocyclic Compound, 36, 2000, 416-420) followed by solid potassium carbonate (12.1 g, finely ground). The reaction mixture was stirred at 50° C. for 20 hours. A further 1.6 g of benzyltriethylammoniumchloride and 4 g of potassium carbonate was added to push the reaction to completion. The reaction mixture was filtered and the filtrate was reduced in vacuo. The residue was diluted with water and extracted with chloroform (3×50 mL). The combined organic phases were washed with brine and dried over sodium sulfate. Filtration and evaporation of the volatiles in vacuo afforded a crude residue which was purified using flash column chromatography (EtOAc/Heptane 2:8) on silica gel to afford the desired 2-(4-Fluoro-phenyl)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (4.25, MS (ES+): 324.3 (MH+)) as a pale yellow oil.

Workup

  1. customthe reaction to completion
  2. filtrationThe reaction mixture was filtered
  3. additionThe residue was diluted with water
  4. extractionextracted with chloroform (3×50 mL)
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationFiltration and evaporation of the volatiles in vacuo
  8. customafforded a crude residue which
  9. customwas purified

Sources & evidence

ORD record
ord-9913af4205a1469ba9a601bf0fe06876
Source dataset
uspto-grants-2012_02
Patent number
US08124636B2

Reaction notes

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