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

HRID 1742229Notes

Reaction equation

HRID 1742229 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-14d834583f9e4799a4c933755670f58a
Source dataset
uspto-grants-1994_08
Patent number
US05338739

Reaction notes

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