Pyrrolidine → 2-(Pyrrolidin-1-yl)-4-amino-m-xylene

HRID 2105289Notes

Reaction equation

HRID 2105289 reaction equation
Br[C:2]1[C:3]([CH3:10])=[C:4]([NH2:9])[CH:5]=[CH:6][C:7]=1[CH3:8].[NH:11]1[CH2:15][CH2:14][CH2:13][CH2:12]1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1>[N:11]1([C:2]2[C:3]([CH3:10])=[C:4]([NH2:9])[CH:5]=[CH:6][C:7]=2[CH3:8])[CH2:15][CH2:14][CH2:13][CH2:12]1

Participants

5

Reactant 3

HCID 31268PyrrolidineHCID 123959063-Bromo-2,4-dimethylanilineHCID 23676156Sodium t-butoxide

Product 1

HCID 204949532-(Pyrrolidin-1-yl)-4-amino-m-xylene

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of the 3-bromo-2,4-dimethylphenylamine (0.6 g, 3.0 mmol) in toluene (10 mL) and pyrrolidine (1.25 mL, 15 mmol) was added sodium-t-butoxide (0.86 g, 9 mmol, 3 eq). The suspension was deoxygenated by passing a stream of N2 gas through the mixture for approximately 5-10 minutes before introducing the tris(dibenzilidene)dipalladium(0) (Pd2(dba)3) (27 mg) and rac-2,2′Bis(diphenylphosphino)-1,1′binaphthyl (BINAP) (25 mg). The nitrogen stream continued 10 minutes before heating at 100° C. overnight. The reaction mixture was cooled, acidified with HCl (2N) and extracted with diethyl ether. The aqueous layer was adjusted basic and re-extracted with ethyl acetate. The organic layer was dried over sodium sulfate, decanted and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, gradient elution with 6:1 to 4:1 hexanes to ethyl acetate) to give the desired 2-(pyrrolidin-1-yl)-4-amino-m-xylene.

Workup

  1. customThe suspension was deoxygenated
  2. customfor approximately 5-10 minutes
  3. additionbefore introducing the tris(dibenzilidene)dipalladium(0) (Pd2(dba)3) (27 mg) and rac-2,2′Bis(diphenylphosphino)-1,1′binaphthyl (BINAP) (25 mg)
  4. temperatureThe reaction mixture was cooled
  5. extractionextracted with diethyl ether
  6. extractionre-extracted with ethyl acetate
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. customdecanted
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by flash chromatography (silica gel, gradient elution with 6:1 to 4:1 hexanes to ethyl acetate)

Sources & evidence

ORD record
ord-b5acaa0dc81246d0a158a98eb406a4c1
Source dataset
uspto-grants-2009_08
Patent number
US07579340B2

Reaction notes

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