Phenol → (R)-2-methyl-1-(3-phenoxy-propyl)-pyrrolidine

HRID 221857Notes

Reaction equation

HRID 221857 reaction equation
[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[CH2:9][CH2:10][CH2:11]Cl.C(=O)([O-])[O-].[K+].[K+].Cl.[CH3:20][C@@H:21]1[CH2:25][CH2:24][CH2:23][NH:22]1.[I-].[Na+]>C(#N)C>[CH3:9][C@@H:10]1[CH2:11][CH2:20][CH2:21][N:22]1[CH2:23][CH2:24][CH2:25][O:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 5

HCID 996PhenolHCID 5238Sodium IodideHCID 80061-Bromo-3-chloropropaneHCID 11430Potassium CarbonateHCID 11147704(2R)-(-)-2-Methylpyrrolidine hydrochloride

Product 1

HCID 67009682(R)-2-methyl-1-(3-phenoxy-propyl)-pyrrolidineYield 77.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a round-bottom flask was added phenol (5.0 g, 53.1 mmol), 1-bromo-3-chloropropane (5.52 mL, 55.8 mmol), potassium carbonate (22.0 g, 159 mmol), and acetonitrile (100 mL). The reaction mixture was heated to reflux for 15 h. To this reaction was then added (R)-2-methyl-pyrrolidine hydrochloride (12.9 g, 106 mmol) and sodium iodide (7.96 g, 53.1 mmol) at room temperature. The reaction was continued to reflux for 24 h. After cooled to room temperature, the reaction was filtered through a pad of Celite eluted with CH2Cl2 (100 mL). The filtrate was concentrated. Purification by column chromatography (5% MeOH in CH2Cl2) to give 9.02 g (77%) of (R)-2-methyl-1-(3-phenoxy-propyl)-pyrrolidine.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 15 h
  3. customat room temperature
  4. temperatureto reflux for 24 h
  5. filtrationthe reaction was filtered through a pad of Celite
  6. washeluted with CH2Cl2 (100 mL)
  7. concentrationThe filtrate was concentrated
  8. customPurification by column chromatography (5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-37af3f5bcbb34f7c9a67be445dd3dbb5
Source dataset
uspto-grants-2012_06
Patent number
US08207168B2

Reaction notes

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