Sodium hydride → 1-{3-[3-(3,4-Dimethoxyphenyl)propoxy]propyl}-pyrrolidine

HRID 908894Notes

Reaction equation

HRID 908894 reaction equation
[OH:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:9][CH2:8][CH2:7][CH2:6]1.[H-].[Na+].S(O[CH2:17][CH2:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[CH:21]=1)(=O)(=O)C.C1OCCOCCOCCOCCOC1>C1(C)C=CC=CC=1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)C>[CH3:29][O:28][C:22]1[CH:21]=[C:20]([CH2:19][CH2:18][CH2:17][O:1][CH2:2][CH2:3][CH2:4][N:5]2[CH2:9][CH2:8][CH2:7][CH2:6]2)[CH:25]=[CH:24][C:23]=1[O:26][CH3:27]

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 3633615-Crown-5HCID 2093421-PyrrolidinepropanolHCID 146225803-(3,4-Dimethoxyphenyl)propan-1-ol mesylate

Product 1

HCID 119785001-{3-[3-(3,4-Dimethoxyphenyl)propoxy]propyl}-pyrrolidineYield 13.1%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Procedure

A To a solution of 1-(3-hydroxypropyl)pyrrolidine (631 mg) in toluene (10 mL) stirred at a temperature close to 0° C. is added sodium hydride (208 mg, 60% wt in paraffin). The mixture is stirred for three hours at room temperature, cooled to a temperature close to 0° C. and 3-(3,4-dimethoxyphenyl)propan-1-ol mesylate (750 mg), 15-crown-5 (30 μL), tetrabutylammonium iodide (8 mg) are added. The mixture is heated at reflux for 30 min, stirred overnight at room temperature and diluted with diethyl oxide. The organic layer is washed twice with water, dried over magnesium sulphate, concentrated under reduced pressure and purified by chromatography over silica gel with dichloromethane/methanol 94/6 as eluent. Fractions containing the expected product are pooled, concentrated under reduced pressure, dissolved in diethyl oxide and salted with a solution of 68.8 mg of oxalic acid in 1 mL of acetone. The precipitate is filtered, rinsed with diethyl oxide and dried to give 110 mg of 1-{3-[3-(3,4-dimethoxyphenyl)propoxy]propyl}-pyrrolidine, oxalate as a solid melting at 78-79° C.

Workup

  1. customclose to 0° C.
  2. temperaturecooled to a temperature
  3. customclose to 0° C.
  4. temperatureThe mixture is heated
  5. temperatureat reflux for 30 min
  6. stirringstirred overnight at room temperature
  7. washThe organic layer is washed twice with water
  8. dry with materialdried over magnesium sulphate
  9. concentrationconcentrated under reduced pressure
  10. custompurified by chromatography over silica gel with dichloromethane/methanol 94/6 as eluent
  11. additionFractions containing the expected product
  12. concentrationconcentrated under reduced pressure
  13. dissolutiondissolved in diethyl oxide
  14. filtrationThe precipitate is filtered
  15. washrinsed with diethyl oxide
  16. customdried

Sources & evidence

ORD record
ord-df4126424de44b38a97cbc1f4c92436e
Source dataset
uspto-grants-2011_09
Patent number
US08017646B2

Reaction notes

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