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

HRID 2268133Notes

Reaction equation

HRID 2268133 reaction equation
[H-].[Al+3].[Na+].[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.O>[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 21862873HCID 21862873, compound

Product 1

HCID 10881101trans 1-Benzyl-4-(4-fluorophenyl)-3-piperidinemethanolYield 81.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
50 °C

Procedure

Sodium aluminium hydride in THF (2.0 ml of a 1M solution) was carefully added to substantially anhydrous magnesium chloride (0.19 g, 1.5% H2O) under nitrogen. 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 (0.60 g) in THF (1.7 ml) was added dropwise over approximately 2 minutes. The reaction mixture was stirred and boiled under reflux for 4 hours. The mixture was cooled to ambient temperature and then stirred in an ice/water bath whilst water (0.1 ml) then 5M sodium hydroxide solution (0.1 ml) and water (0.1 ml) were added. The suspension was diluted with THF (5 ml) and the mixture filtered. The residue was washed with THF (3×5 ml) and the combined filtrate and washings were evaporated under reduced pressure to give a yellow oil (0.49 g). This oil was analysed by GLC, Chiral HPLC and 1H nmr using the conditions described above. Starting material 13.2% was still present in the product as analysed by GLC. The amount of desfluoro compound as determined by HPLC was less than 0.1%.

Workup

  1. stirringThe reaction mixture was stirred
  2. temperatureunder reflux for 4 hours
  3. temperatureThe mixture was cooled to ambient temperature
  4. filtrationthe mixture filtered
  5. washThe residue was washed with THF (3×5 ml)
  6. customthe combined filtrate and washings were evaporated under reduced pressure

Sources & evidence

ORD record
ord-3e5b2d865d2647a0acc1b15ba4c76e55
Source dataset
uspto-grants-2001_12
Patent number
US06326496B1

Reaction notes

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