Water → 78383-61-6

HRID 443426Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C([Li])CCC.[F:13][C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=1)[CH:17]=[O:18].O>CCOCC.CCCCCCC>[F:13][C:14]1[CH:15]=[C:16]([CH:17]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=2)[OH:18])[CH:19]=[CH:20][CH:21]=1

Participants

Conditions

Temperature: -40 °C

Procedure

A solution of 17.4 g of 2-bromopyridine in 40 ml of ether is added slowly with stirring to 75 ml of commercial n-butyl lithium in heptane and 100 ml of ether at -50° to -40° C. under a nitrogen atmosphere. After stirring another 0.25 hours at -40° C., a solution of 12.5 g of 3-fluorobenzaldehyde in 30 ml of ether is added dropwise and the mixture is allowed to warm to room temperature. After stirring 3 hours, 100 ml of water is added, the organic layer is separated, dried over MgSO4 and the solvent is evaporated. The residue is chromatographed over silica gel in acetonitrile to obtain alpha-(3-fluorophenyl)-2-pyridinemethanol; mp 80°-82° C., after recrystallization from cyclohexane. The alpha-(3-fluorophenyl)-2-pyridinemethanol is hydrogenated at about 50 lbs. p.s.i. in methanol-acetic acid in the presence of 10% Rh/C. The reaction mixture is filtered, the solvent evaporated from the filtrate, and the residue dissolved in methylene dichloride and shaken with concentrated sodium hydroxide. The organic layer is separated, dried, and concentrated to obtain the desired alpha-(3-fluorophenyl)-2-piperidinemethanol; mp 146°-148° C.

Workup

temperatureto warm to room temperature
stirringAfter stirring 3 hours
customthe organic layer is separated
dry with materialdried over MgSO4
customthe solvent is evaporated
customThe residue is chromatographed over silica gel in acetonitrile

Sources & evidence

ORD record: ord-fd7992e9a99346d197a13c11aa075c49
Source dataset: uspto-grants-1981_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04260623

Reaction notes

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