1-Benzyl-4-piperidone → 1-Benzyl-4-[4-(tetrahydropyran-2-yloxy)phenyl]piperidin-4-ol

HRID 856109Notes

Reaction equation

HRID 856109 reaction equation
Br[C:2]1[CH:14]=[CH:13][C:5]([O:6][CH:7]2[CH2:12][CH2:11][CH2:10][CH2:9][O:8]2)=[CH:4][CH:3]=1.C([Li])CCC.[CH2:20]([N:27]1[CH2:32][CH2:31][C:30](=[O:33])[CH2:29][CH2:28]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[Cl-].[NH4+]>C1COCC1>[CH2:20]([N:27]1[CH2:32][CH2:31][C:30]([C:2]2[CH:14]=[CH:13][C:5]([O:6][CH:7]3[CH2:12][CH2:11][CH2:10][CH2:9][O:8]3)=[CH:4][CH:3]=2)([OH:33])[CH2:29][CH2:28]1)[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

6

Reactant 4

HCID 192201-Benzyl-4-piperidoneHCID 25517Ammonium ChlorideHCID 46464362-(4-Bromophenoxy)tetrahydro-2H-pyranHCID 178418339Butyllithium

Product 1

HCID 230814111-Benzyl-4-[4-(tetrahydropyran-2-yloxy)phenyl]piperidin-4-olYield 51.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 2-(4-bromophenoxy)-tetrahydropyran (7.2 g, 28 mmol) in THF (70 ml) was cooled to −60° C., to which n-butyl lithium (1.53 M) hexane solution (20 ml, 30.8 mmol) was added dropwise, and the mixture was stirred for 30 minutes. Then, a solution of 1-benzyl-4-piperidone (5.3 g, 28 mmol) in THF (20 ml) was added dropwise to this mixture, which was stirred for 3 hours while being allowed to reach a temperature of 0° C. Saturated ammonium chloride aqueous solution was added to the reaction mixture, which was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=20/1) to afford 1-benzyl-4-[4-(tetrahydropyran-2-yloxy)phenyl]piperidin-4-ol (5.27 g, yield 51%) as an orange-colored oil.

Workup

  1. additionwas added dropwise
  2. stirringwas stirred for 3 hours
  3. customa temperature of 0° C
  4. extractionwas extracted with ethyl acetate
  5. washThe extract was washed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=20/1)

Sources & evidence

ORD record
ord-e1002e379b2d4e90970c1b512412b25f
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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