Pyrrolidine → 1-(4-Nitro-2-methoxybenzyl)pyrrolidine

HRID 367250Notes

Reaction equation

HRID 367250 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([O:11][CH3:12])[CH:5]=1)([O-:3])=[O:2].Br[N:14]1[C:18](=O)[CH2:17][CH2:16][C:15]1=O.N1CCCC1>N(C(C)(C)C#N)=NC(C)(C)C#N.C(Cl)(Cl)(Cl)Cl>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)=[C:6]([O:11][CH3:12])[CH:5]=1)([O-:3])=[O:2]

Participants

6

Reactant 3

HCID 31268PyrrolidineHCID 67184N-bromobutanimideHCID 83159Benzene, 2-methoxy-1-methyl-4-nitro-

Product 1

HCID 232877701-(4-Nitro-2-methoxybenzyl)pyrrolidineYield 80%

Reagents, catalysts & solvents 2

HCID 6547AzobisisobutyronitrileCatalystHCID 5943Carbon TetrachlorideSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 4-nitro-2-methoxytoluene (5 g, 30 mmol), N-bromosuccinimide (5.3 g, 30 mmol), azobisisobutyronitrile (AIBN, 10 mg) and CCl4 was refluxed for 60 h. The reaction mixture was cooled to 0° C., filtered through diatomaceous earth and concentrated under vacuum. The resulting oil was redissolved in THF (50 mL) and added portionwise to a cold (0° C.) stirred solution of pyrrolidine (10.65 g, 150 mmol). Afterwards, the cooling bath was removed and the reaction was stirred at ambient temperature for 1 h. It was then concentrated to an oil, diluted with 100 mL saturated aqueous NaHCO3 and 50 mL brine. Following extraction three times with 125 mL EtOAc, the combined organic layer was dried over MgSO4 and concentrated to 6.5 g of an oil. Purification by chromatography (SiO2 ; 30% EtOAc in hexanes) yielded 5.7 g (24 mmol, 80%) of the desired compound as an oil.

Workup

  1. temperaturewas refluxed for 60 h
  2. filtrationfiltered through diatomaceous earth
  3. concentrationconcentrated under vacuum
  4. dissolutionThe resulting oil was redissolved in THF (50 mL)
  5. additionadded portionwise to a cold (0° C.)
  6. customAfterwards, the cooling bath was removed
  7. concentrationIt was then concentrated to an oil
  8. additiondiluted with 100 mL saturated aqueous NaHCO3 and 50 mL brine
  9. extractionextraction three times with 125 mL EtOAc
  10. dry with materialthe combined organic layer was dried over MgSO4
  11. concentrationconcentrated to 6.5 g of an oil
  12. customPurification by chromatography (SiO2 ; 30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-0ff964e379a243c99c3aa4f7a4cf7317
Source dataset
uspto-grants-2000_10
Patent number
US06133262

Reaction notes

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