4-Heptanone → 1-{3-[4-(1-Hydroxy-1-propylbutyl)-phenoxy]propyl}piperidine

HRID 657613Notes

Reaction equation

HRID 657613 reaction equation
[CH3:1][CH2:2][CH2:3][C:4](=[O:8])[CH2:5][CH2:6][CH3:7].[N:9]1([CH2:15][CH2:16][CH2:17][O:18][C:19]2[CH:24]=[CH:23][C:22]([Mg]Br)=[CH:21][CH:20]=2)[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1>O1CCCC1>[OH:8][C:4]([C:22]1[CH:23]=[CH:24][C:19]([O:18][CH2:17][CH2:16][CH2:15][N:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:20][CH:21]=1)([CH2:5][CH2:6][CH3:7])[CH2:3][CH2:2][CH3:1]

Participants

4

Reactant 2

HCID 312464-HeptanoneHCID 178419639HCID 178419639, compound

Product 1

HCID 119787351-{3-[4-(1-Hydroxy-1-propylbutyl)-phenoxy]propyl}piperidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-heptanone (471 mg) in tetrahydrofuran (4 mL) is added a solution of 4-(3-piperidinopropoxy)phenylmagnesium bromide in tetrahydrofuran (11 mL, 3.3 mmol). The mixture is stirred overnight at room temperature and quenched at 0° C. with a saturated aqueous solution of ammonium chloride (20 mL). The solution is extracted with ethyl acetate (20 mL) and the organic layer is washed with a saturated aqueous solution of ammonium chloride (20 mL), dried over magnesium sulphate, concentrated under reduced pressure and purified by chromatography over silica gel with a gradient dichloromethane/methanol from 98/2 to 95/5 as eluent. Fractions containing the expected product are pooled and concentrated under reduced pressure to give 1-{3-[4-(1-hydroxy-1-propylbutyl)-phenoxy]propyl}piperidine as a yellow oil. Salt formation with oxalic acid in ethanol and precipitation with diethyl oxide affords 1-{3-[4-(1-hydroxy-1-propylbutyl)-phenoxy]propyl}piperidine, oxalate as a white solid melting at 118° C.

Workup

  1. customquenched at 0° C. with a saturated aqueous solution of ammonium chloride (20 mL)
  2. extractionThe solution is extracted with ethyl acetate (20 mL)
  3. washthe organic layer is washed with a saturated aqueous solution of ammonium chloride (20 mL)
  4. dry with materialdried over magnesium sulphate
  5. concentrationconcentrated under reduced pressure
  6. custompurified by chromatography over silica gel with a gradient dichloromethane/methanol from 98/2 to 95/5 as eluent
  7. additionFractions containing the expected product
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-efe248fd6244475da7956774265ec4e2
Source dataset
uspto-grants-2011_12
Patent number
US08076329B2

Reaction notes

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