Sodium Hydroxide → trans 1-Benzyl-4-(4-fluorophenyl)-3-piperidinemethanol

HRID 2268134Notes

Reaction equation

HRID 2268134 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl-].[Mg+2].[Cl-].[CH2:10]([N:17]1[CH2:22][CH:21]=[C:20]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[CH:19]([CH2:30][OH:31])[CH2:18]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[OH-].[Na+]>C1COCC1.C1(C)C=CC=CC=1>[CH2:10]([N:17]1[CH2:22][CH2:21][C@@H:20]([C:23]2[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=2)[C@H:19]([CH2:30][OH:31])[CH2:18]1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 5360315Magnesium ChlorideHCID 9912522(+)-4-(4-Fluorophenyl)-1,2,3,6-tetrahydro-1-(phenylmethyl)-3-pyridinemethanolHCID 21226445Aluminium lithium hydride

Product 1

HCID 10881101trans 1-Benzyl-4-(4-fluorophenyl)-3-piperidinemethanol

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
50 °C

Procedure

Lithium aluminium hydride in THF (7.24 ml of a 1M solution) was carefully added to substantially anhydrous magnesium chloride (0.698 g), in THF (32 ml) with stirring under nitrogen keeping the temperature below 20° C. The mixture was stirred and heated to 50° C. and then a solution of (+)-1-benzyl-3-hydroxymethyl-4-(4-fluorophenyl)-1,2,3,6-tetrahydropyridine (2.15 g, preparable as described in WO96/36636) in THF (3.92 ml) and toluene (2.32 ml) was added dropwise over approximately 30 minutes. The reaction mixture was stirred and boiled under reflux for 4.0 hours. The mixture was cooled to 0-5° C. in an ice/water bath whilst sodium hydroxide solution (2.48 g, 5%w/w) was added. The suspension was filtered. The residue was washed with THF (8 ml) and the combined filtrate and washings were evaporated under reduced pressure to give a yellow oil. This oil was analysed by GLC, Chiral HPLC and 1H nmr. The title compound contained 0.24% of the desfluoro compound.

Workup

  1. stirringThe mixture was stirred
  2. stirringThe reaction mixture was stirred
  3. temperatureunder reflux for 4.0 hours
  4. additionwas added
  5. filtrationThe suspension was filtered
  6. washThe residue was washed with THF (8 ml)
  7. customthe combined filtrate and washings were evaporated under reduced pressure
  8. customto give a yellow oil

Sources & evidence

ORD record
ord-f95dc9f180e947118568be51c411920b
Source dataset
uspto-grants-2001_12
Patent number
US06326496B1

Reaction notes

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