Sodium Hydroxide → trans 1-Benzyl-4-(4-fluorophenyl)-3-piperidinemethanol
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.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]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 50 °C
Procedure
Lithium 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, preparation given in WO96136636) in THF (1.7 ml) was added dropwise over approximately 2 minutes. The reaction mixture was stirred and boiled under reflux for 4.2 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.
Workup
- stirringThe reaction mixture was stirred
- temperatureunder reflux for 4.2 hours
- temperatureThe mixture was cooled to ambient temperature
- filtrationthe mixture filtered
- washThe residue was washed with THF (3×5 ml)
- customthe combined filtrate and washings were evaporated under reduced pressure
Sources & evidence
- ORD record
- ord-8cac6582eb4d41a5a5c8e8a097d34b83
- Source dataset
- uspto-grants-2001_12
- Patent number
- US06326496B1
Reaction notes
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