1-Benzyl-4-piperidone → 2-[4-Hydroxy-1-(phenylmethyl)-4-piperidinyl]-3-pyridinemethanol

HRID 1663335Notes

Reaction equation

HRID 1663335 reaction equation
Br[C:2]1[C:7]([CH2:8][OH:9])=[CH:6][CH:5]=[CH:4][N:3]=1.CC([Mg]Cl)C.[CH2:15]([N:22]1[CH2:27][CH2:26][C:25](=[O:28])[CH2:24][CH2:23]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>O1CCCC1>[CH2:15]([N:22]1[CH2:27][CH2:26][C:25]([OH:28])([C:2]2[C:7]([CH2:8][OH:9])=[CH:6][CH:5]=[CH:4][N:3]=2)[CH2:24][CH2:23]1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

5

Reactant 3

HCID 192201-Benzyl-4-piperidoneHCID 14761460(2-Bromopyridin-3-yl)methanolHCID 178418918HCID 178418918, compound

Product 1

HCID 597568262-[4-Hydroxy-1-(phenylmethyl)-4-piperidinyl]-3-pyridinemethanolYield 17.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4.0 g (21 mmol) (2-bromo-pyridin-3-yl)-methanol in 105 ml dry tetrahydrofuran were added 22 ml (45 mmol) 2-propylmagnesium chloride solution (2.0 M in tetrahydrofuran). The reaction mixture was heated at reflux for 2 h. A solution of 3.8 g (21 mmol) 1-benzyl-4-piperidone in 22 ml tetrahydrofuran was added dropwise at a temperature of approximately 65° C. The reaction mixture was heated at reflux for 3 h and then quenched with water. The aqueous layer was basified to pH 9 with aqueous 1 M sodium hydroxide and extracted with three portions of ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo. Flash-chromatography gave the title compound (1.1 g, 17%) as a brown solid.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 2 h
  3. temperatureThe reaction mixture was heated
  4. temperatureat reflux for 3 h
  5. customquenched with water
  6. extractionextracted with three portions of ethyl acetate
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2013057e3ee4428d8f5932b3bc313e40
Source dataset
uspto-grants-2011_10
Patent number
US08034937B2

Reaction notes

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