O-Toluidine → N-(2-Methylphenyl)pyrrolidine

HRID 1925739Notes

Reaction equation

HRID 1925739 reaction equation
[NH2:1][C:2]1[C:3]([CH3:8])=[CH:4][CH:5]=[CH:6][CH:7]=1.C(=O)([O-])[O-].[Na+].[Na+].Br[CH2:16][CH2:17][CH2:18][CH2:19]Br>CO.O>[C:3]1([CH3:8])[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[N:1]1[CH2:19][CH2:18][CH2:17][CH2:16]1

Participants

6

Reactant 3

HCID 7242O-ToluidineHCID 80561,4-DibromobutaneHCID 10340Sodium Carbonate

Product 1

HCID 142531N-(2-Methylphenyl)pyrrolidineYield 41.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of o-toluidine (2.0 g; 18.7 mmol) in methanol (62 mL) was added sodium carbonate (4.95 g; 46.75 mmol) followed by 1,4-dibromobutane (4.85 g; 22.4 mmol). The resulting mixture was stirred at 50° C. under a nitrogen atmosphere overnight and then diluted with water and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by automated silica gel column chromatography (Biotage®) eluting with ethyl acetate/hexanes (0 to 40% v/v over 900 mL gradient elution) to yield the title product as a dark yellow-orange oil (1.24 g).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude residue was purified by automated silica gel column chromatography (Biotage®)
  6. washeluting with ethyl acetate/hexanes (0 to 40% v/v over 900 mL gradient elution)

Sources & evidence

ORD record
ord-90640e867e4f4781b5da5988b85986ff
Source dataset
uspto-grants-2012_05
Patent number
US08178699B2

Reaction notes

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