Ethyl p-methylbenzenesulfonate → Methyl (3S*,4R*)-4-(2,4-difluorophenyl)-1-ethylpyrrolidine-3-carboxylate

HRID 1992687Notes

Reaction equation

HRID 1992687 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@H:9]1[CH2:13][NH:12][CH2:11][C@H:10]1[C:14]([O:16][CH3:17])=[O:15].S(C1C=CC(C)=CC=1)(O[CH2:22][CH3:23])(=O)=O.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@H:9]1[CH2:13][N:12]([CH2:22][CH3:23])[CH2:11][C@H:10]1[C:14]([O:16][CH3:17])=[O:15]

Participants

5

Reactant 3

HCID 6638Ethyl p-methylbenzenesulfonateHCID 11430Potassium CarbonateHCID 59130986methyl (3S,4R)-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylate

Product 1

HCID 59130979Methyl (3S*,4R*)-4-(2,4-difluorophenyl)-1-ethylpyrrolidine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of methyl (3S,4R)-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylate from Preparation 31 (500 mg, 2.07 mmol), ethyl tosylate (519 mg, 2.59 mmol) and potassium carbonate (573 mg, 4.15 mmol) were heated in acetonitrile at 70° C. for 16 hours under nitrogen. The reaction mixture was then cooled to room temperature and concentrated in vacuo. The residue was dissolved in dichloromethane (30 ml) and partitioned with saturated aqueous sodium bicarbonate (30 ml). The organic layer was then washed with brine (20 ml), dried over magnesium sulfate, filtered, and the solvent was removed in vacuo. The above procedure was performed in duplicate. The crude products from the two reactions were then combined and purified by column chromatography on silica eluting with dichloromethane:methanol (99:1) to give the title compound as a pale yellow oil, 968 mg.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in dichloromethane (30 ml)
  3. custompartitioned with saturated aqueous sodium bicarbonate (30 ml)
  4. washThe organic layer was then washed with brine (20 ml)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customthe solvent was removed in vacuo
  8. custompurified by column chromatography on silica eluting with dichloromethane:methanol (99:1)

Sources & evidence

ORD record
ord-1e73c64a804d47e88b0b8f92c955d99e
Source dataset
uspto-grants-2010_01
Patent number
US07649002B2

Reaction notes

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