Potassium Iodide → 1-[gamma-(2-Methyl-4-fluorobenzoyl)-propyl]-4-(3-trifluoromethylphenyl)-4-hydroxypiperidine

HRID 1659322Notes

Reaction equation

HRID 1659322 reaction equation
Cl[CH2:2][CH2:3][CH2:4][C:5]1([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=2[CH3:17])[O:9]CCO1.[F:18][C:19]([F:34])([F:33])[C:20]1[CH:21]=[C:22]([C:26]2([OH:32])[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)[CH:23]=[CH:24][CH:25]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CN(C)C=O>[CH3:17][C:11]1[CH:12]=[C:13]([F:16])[CH:14]=[CH:15][C:10]=1[C:5]([CH2:4][CH2:3][CH2:2][N:29]1[CH2:28][CH2:27][C:26]([C:22]2[CH:23]=[CH:24][CH:25]=[C:20]([C:19]([F:18])([F:33])[F:34])[CH:21]=2)([OH:32])[CH2:31][CH2:30]1)=[O:9]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 752554-[3-(Trifluoromethyl)phenyl]-4-piperidinolHCID 130029542-(3-Chloropropyl)-2-(4-fluoro-2-methylphenyl)-1,3-dioxolane

Product 1

HCID 130029551-[gamma-(2-Methyl-4-fluorobenzoyl)-propyl]-4-(3-trifluoromethylphenyl)-4-hydroxypiperidine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3 g of 4-chloro-1-(2-methyl-4-fluorophenyl)-1,1-ethylenedioxybutane, 2.5 g of 4-(3-trifluoromethylphenyl)-4-hydroxypiperidine, 1.4 g of anhydrous potassium carbonate, 0.05 g of potassium iodide and 30 ml of dimethylformamide was refluxed for 3 hours. The resulting mixture was poured into ice water and was extracted with ethyl acetate. The extract was washed with water, dried over anhydrous sodium sulfate and concentrated in vacuo. To the residual oil were added 60 ml of methanol, 21 ml of water and 10.5 ml of concentrated hydrochloric acid. The mixture was refluxed for 50 minutes and concentrated in vacuo. The residual oil was made alkaline with 28% aqueous ammonia and extracted with ethyl acetate. The extract was washed with water, dried over anhydrous sodium sulfate and concentrated. The residual solid was recrystallized from isopropyl ether to give 1-[γ-(2-methyl-4-fluorobenzoyl)-propyl]-4-(3-trifluoromethylphenyl)-4-hydroxypiperidine, melting at about 63.5°-64.5° C.

Workup

  1. temperaturewas refluxed for 3 hours
  2. extractionwas extracted with ethyl acetate
  3. washThe extract was washed with water
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. additionTo the residual oil were added 60 ml of methanol, 21 ml of water and 10.5 ml of concentrated hydrochloric acid
  7. temperatureThe mixture was refluxed for 50 minutes
  8. concentrationconcentrated in vacuo
  9. extractionextracted with ethyl acetate
  10. washThe extract was washed with water
  11. dry with materialdried over anhydrous sodium sulfate
  12. concentrationconcentrated
  13. customThe residual solid was recrystallized from isopropyl ether

Sources & evidence

ORD record
ord-7e2b3d9d70b14b3bb1dc33db55530f9b
Source dataset
uspto-grants-1981_12
Patent number
US04303663

Reaction notes

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