2-Methylpyrrolidine → HCID 178426194, compound

HRID 657676Notes

Reaction equation

HRID 657676 reaction equation
Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C@H:12]2[CH2:17][CH2:16][C@H:15]([OH:18])[CH2:14][CH2:13]2)=[CH:8][CH:7]=1.[Na].[CH3:20][CH:21]1[CH2:25][CH2:24][CH2:23][NH:22]1>C(#N)C>[OH:18][C@H:15]1[CH2:16][CH2:17][C@H:12]([C:9]2[CH:10]=[CH:11][C:6]([O:5][CH2:4][CH2:3][CH2:2][N:22]3[CH2:23][CH2:24][CH2:25][CH:21]3[CH3:20])=[CH:7][CH:8]=2)[CH2:13][CH2:14]1

Participants

5

Reactant 3

HCID 130032-MethylpyrrolidineHCID 5360545SodiumHCID 178521552HCID 178521552, compound

Product 1

HCID 178426194HCID 178426194, compoundYield 25.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A A mixture of trans-4-[4-(3-chloropropoxy)phenyl]cyclohexanol (403 mg), sodium hydrogenocarbonate (252 mg) potassium iodide (10 mg) and 2-methylpyrrolidine (153 mg) in acetonitrile (10 mL) is heated for 24 hours under reflux, then concentrated under reduced pressure. The residue is dissolved in ethyl acetate (25 mL). The organic phase is washed with water (5 mL), dried over magnesium sulfate, concentrated under reduced pressure and purified by chromatography over silica gel (eluent dichloromethane/methanol from 98/2 to 90/10). Fractions containing the expected product are pooled and concentrated under reduced pressure to give 120 mg of 1-{3-[trans-4-(4-hydroxycyclohexyl)phenoxy]propyl}-2-methylpyrrolidine as a white solid melting at 80° C.

Workup

  1. temperatureis heated for 24 hours
  2. temperatureunder reflux
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue is dissolved in ethyl acetate (25 mL)
  5. washThe organic phase is washed with water (5 mL)
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. custompurified by chromatography over silica gel (eluent dichloromethane/methanol from 98/2 to 90/10)
  9. additionFractions containing the expected product
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0db6678ee3c4410d87ff93019ea046ad
Source dataset
uspto-grants-2011_12
Patent number
US08076329B2

Reaction notes

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