4-Fluorobenzonitrile → cis-4-(4-Cyanophenoxy)-1-methyl-3-phenylpiperidine

HRID 1106322Notes

Reaction equation

HRID 1106322 reaction equation
[H-].[Na+].[CH3:3][N:4]1[CH2:9][CH2:8][C@H:7]([OH:10])[C@H:6]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:5]1.[H][H].F[C:20]1[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][CH:21]=1>CN(C=O)C.O>[C:24]([C:23]1[CH:26]=[CH:27][C:20]([O:10][C@H:7]2[CH2:8][CH2:9][N:4]([CH3:3])[CH2:5][C@H:6]2[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:21][CH:22]=1)#[N:25]

Participants

7

Reactant 4

HCID 145174-FluorobenzonitrileHCID 24758Sodium hydrideHCID 12788379cis-1-Methyl-3-phenyl-4-piperidinolHCID 178418361HCID 178418361, compound

Product 1

HCID 12788395cis-4-(4-Cyanophenoxy)-1-methyl-3-phenylpiperidine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
80 °C

Procedure

A mixture of 0.31 g of sodium hydride, 2.48 g of cis-1-methyl-3-phenyl-4-piperidinol of Example 22 and 20 ml of dry DMF is slowly heated to 80° C. When hydrogen evolution is no longer observed, the mixture is cooled to 3° C. and a solution of 1.73 g of p-fluorobenzonitrile in 10 ml of DMF is added. The mixture is stirred for 18 hours at room temperature under nitrogen, poured into 100 ml of distilled water, and extracted with chloroform. The chloroform extracts are dried over anhydrous Na2SO4 and concentrated in vacuo to an oil containing DMF. This oil is partitioned between saturated aqueous NaCl solution and ether. The aqueous phase is extracted with ether, and the ether extracts are then washed with water and dried over anhydrous Na2SO4. Concentration in vacuo affords an oil which crystallizes while under high vacuum. This material is chromatographed on silica gel, using 25% methanol/acetone solution to obtain cis-4-(4-cyanophenoxy)-1-methyl-3-phenylpiperidine, m.p. s 138°, 139°-141° C.

Workup

  1. temperaturethe mixture is cooled to 3° C.
  2. extractionextracted with chloroform
  3. dry with materialThe chloroform extracts are dried over anhydrous Na2SO4
  4. concentrationconcentrated in vacuo to an oil
  5. additioncontaining DMF
  6. customThis oil is partitioned between saturated aqueous NaCl solution and ether
  7. extractionThe aqueous phase is extracted with ether
  8. washthe ether extracts are then washed with water
  9. dry with materialdried over anhydrous Na2SO4
  10. concentrationConcentration in vacuo
  11. customaffords an oil which
  12. customcrystallizes while under high vacuum
  13. customThis material is chromatographed on silica gel

Sources & evidence

ORD record
ord-18f90dbbb44b494ebffac732b093f83f
Source dataset
uspto-grants-1982_01
Patent number
US04312876

Reaction notes

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