Sodium hydride → 2-(3-Methoxyphenyl)-1-(4-pyridinylmethyl)pyrrolidine

HRID 233015Notes

Reaction equation

HRID 233015 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]2[CH2:13][CH2:12][CH2:11][NH:10]2)[CH:6]=[CH:7][CH:8]=1.[H-].[Na+].Cl.[N:17]1[CH:22]=[CH:21][C:20]([CH2:23]Cl)=[CH:19][CH:18]=1>ClCCl.O.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]2[CH2:13][CH2:12][CH2:11][N:10]2[CH2:23][C:20]2[CH:21]=[CH:22][N:17]=[CH:18][CH:19]=2)[CH:6]=[CH:7][CH:8]=1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 745704-(Chloromethyl)pyridinium chlorideHCID 36138242-(3-Methoxyphenyl)pyrrolidine

Product 1

HCID 233612992-(3-Methoxyphenyl)-1-(4-pyridinylmethyl)pyrrolidineYield 70%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 2-(3-methoxyphenyl)pyrrolidine (5.42 g) in dry dichloromethane (153 ml) was added sodium hydride (97%, 1.69 g) followed by 4-picolyl chloride hydrochloride (5.26 g), under nitrogen, at 0° C. The reaction mixture was stirred for 15 hrs at ambient temperature and diluted with water and ethyl acetate. The layers were separated, and the aqueous phase was extracted with ethyl acetate (4 times). The combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The residue was purified by flash column chromatography (silica gel, 2% triethylamine/ether). The appropriate fractions were collected and evaporated to afford 5.70 g (70%) of 2-(3-methoxyphenyl)-1-(4-pyridinylmethyl)pyrrolidine.

Workup

  1. customThe layers were separated
  2. extractionthe aqueous phase was extracted with ethyl acetate (4 times)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated
  7. customThe residue was purified by flash column chromatography (silica gel, 2% triethylamine/ether)
  8. customThe appropriate fractions were collected
  9. customevaporated

Sources & evidence

ORD record
ord-01246d862b67499c8ae5c698d9634584
Source dataset
uspto-grants-1997_01
Patent number
US05591856

Reaction notes

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