1-Benzylpiperidin-4-ol → 2-[(1-Benzylpiperidin-4-yl)oxy]-3-methylpyridine

HRID 1053855Notes

Reaction equation

HRID 1053855 reaction equation
CC(C)([O-])C.[K+].[CH2:7]([N:14]1[CH2:19][CH2:18][CH:17]([OH:20])[CH2:16][CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.F[C:22]1[C:27]([CH3:28])=[CH:26][CH:25]=[CH:24][N:23]=1>CS(C)=O>[CH2:7]([N:14]1[CH2:19][CH2:18][CH:17]([O:20][C:22]2[C:27]([CH3:28])=[CH:26][CH:25]=[CH:24][N:23]=2)[CH2:16][CH2:15]1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

5

Reactant 3

HCID 784611-Benzylpiperidin-4-olHCID 2427222-Fluoro-3-methylpyridineHCID 23665647Potassium tert-butoxide

Product 1

HCID 577538832-[(1-Benzylpiperidin-4-yl)oxy]-3-methylpyridineYield 85%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

Potassium tert-butoxide (1.08 g, 8.62 mmol) was added to a solution of 1-benzyl-4-hydroxypiperidine (1.5 g, 7.84 mmol) in dimethylsulfoxide (5 mL) and the mixture was stirred at room temperature for 1 hour. 2-Fluoro-3-methylpyridine (957 mg, 8.62 mmol) was then added and the reaction mixture was stirred at room temperature for 3 hours. The mixture was partitioned between ethyl acetate and water, and the organic layer was separated and washed with sodium hydrogen carbonate solution and brine. The organic solution was then dried over magnesium sulfate concentrated in vacuo and the residue was purified by column chromatography on silica gel, eluting with dichloromethane:methanol, 100:0 to 70:30, to afford the title compound as a solid in 85% yield, 1.9 g. 1H NMR (CDCl3, 400 MHz): 1.79-1.94 (m, 2H), 1.98-2.09 (m, 2H), 2.17 (s, 3H), 2.37-2.47 (m, 2H), 2.68-2.77 (m, 2H), 3.61-3.51 (bs, 2H), 5.12-5.20 (m, 1H), 6.74 (m, 1H), 7.24-7.37 (m, 6H), 7.95 (m, 1H); LRMS APCI m/z 283 [M+H]+.

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 3 hours
  2. customThe mixture was partitioned between ethyl acetate and water
  3. customthe organic layer was separated
  4. washwashed with sodium hydrogen carbonate solution and brine
  5. dry with materialThe organic solution was then dried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customthe residue was purified by column chromatography on silica gel
  8. washeluting with dichloromethane

Sources & evidence

ORD record
ord-3796f43ecbb64f0bbc6cf0b8fc88ec00
Source dataset
uspto-grants-2016_07
Patent number
US09394278B2

Reaction notes

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