1-Benzyl-4-piperidone → 1'-Benzyl-4-hydroxymethyl-2',3',5',6'-tetrahydro-1'H-[3,4']bipyridinyl-4'-ol

HRID 1663338Notes

Reaction equation

HRID 1663338 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[CH2:8][OH:9].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[CH:3]=[N:4][CH:5]=[CH:6][C:7]=2[CH2:8][OH:9])[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 46840038(3-Bromopyridin-4-yl)methanolHCID 178418918HCID 178418918, compound

Product 1

HCID 597568131'-Benzyl-4-hydroxymethyl-2',3',5',6'-tetrahydro-1'H-[3,4']bipyridinyl-4'-olYield 16%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1.9 g (10 mmol) (3-bromo-pyridin-4-yl)-methanol in 50 ml dry tetrahydrofuran were added 11 ml (21 mmol) 2-propylmagnesium chloride solution (2.0 M in tetrahydrofuran). The reaction mixture was heated at reflux for 2 h. A solution of 1.9 g (10 mmol) 1-benzyl-4-piperidone in 5 ml tetrahydrofuran was added dropwise at a temperature of approximately 65° C. The reaction mixture was heated at reflux for 2 h and then quenched with water. The tetrahydrofuran was evaporated. The aqueous layer was basified to pH 10 with aqueous 2 M sodium hydroxide solution and extracted with three portions of tert-butyl methyl ether. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo. Flash-chromatography gave the title compound (0.47 g, 16%) 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 2 h
  5. customquenched with water
  6. customThe tetrahydrofuran was evaporated
  7. extractionextracted with three portions of tert-butyl methyl ether
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f9a8254b28994f82965f52686c30568f
Source dataset
uspto-grants-2011_10
Patent number
US08034937B2

Reaction notes

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