Acetonitrile → (2R)-1-[3-(4-bromo-2-fluorophenoxy)propyl]-2-methylpyrrolidine

HRID 215778Notes

Reaction equation

HRID 215778 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5](O)=[C:4]([F:9])[CH:3]=1.[C:10](=[O:13])([O-])[O-].[Cs+].[Cs+].[C:16](#[N:18])[CH3:17]>ClCCCN1CCC[C@H]1C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:13][CH2:10][CH2:17][CH2:16][N:18]2[CH2:6][CH2:7][CH2:2][C@H:3]2[CH3:4])=[C:4]([F:9])[CH:3]=1

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 10796Cesium carbonateHCID 27249814-Bromo-2-fluorophenol

Product 1

HCID 59541739(2R)-1-[3-(4-bromo-2-fluorophenoxy)propyl]-2-methylpyrrolidineYield 94%

Reagents, catalysts & solvents 1

HCID 55301078(2R)-1-(3-chloropropyl)-2-methylpyrrolidineSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of 4-bromo-2-fluorophenol (0.57 g) and cesium carbonate (1.6 g) in acetonitrile (2.5 mL), (2R)-1-(3-chloropropyl)-2-methylpyrrolidine obtained in Example 62-(1) (0.40 g) was added and the mixture was heated to 100° C., at which it was stirred for 4 hours. The reaction mixture was cooled to room temperature and filtered to remove insoluble materials, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by NH-type silica gel column chromatography (eluting solvent: n-hexane:ethyl acetate=10:1 to 3:1) to give the titled compound (0.73 g, 94%) as a yellow oil.

Workup

  1. additionwas added
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationfiltered
  4. customto remove insoluble materials
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe resulting residue was purified by NH-type silica gel column chromatography (eluting solvent: n-hexane:ethyl acetate=10:1 to 3:1)

Sources & evidence

ORD record
ord-3d59b6b8ee284f9c86c09340b23b457f
Source dataset
uspto-grants-2012_06
Patent number
US08193176B2

Reaction notes

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