Potassium Iodide → HCID 20356964, compound

HRID 2083661Notes

Reaction equation

HRID 2083661 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2([OH:15])[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:5][CH:4]=1.[I-].[K+].[OH-].[K+].[CH3:20][O:21][C:22]([O:34][CH3:35])([C:27]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=1)[CH2:23][CH2:24][CH2:25]Cl>C1(C)C=CC=CC=1.O>[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2([OH:15])[CH2:10][CH2:11][N:12]([CH2:25][CH2:24][CH2:23][C:22]([C:27]3[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=3)([O:34][CH3:35])[O:21][CH3:20])[CH2:13][CH2:14]2)=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 14797Potassium HydroxideHCID 30474564-Piperidinol, 4-(4-chlorophenyl)-, hydrochlorideHCID 112766731-(4-CHLORO-1,1-DIMETHOXYBUTYL)-4-FLUOROBENZENE

Product 1

HCID 20356964HCID 20356964, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent2×

Conditions

Temperature
55 °C

Procedure

A stirred slurry of 120.0 parts 4-(4-chlorophenyl)piperidin-4-ol hydrochloride and 40.0 parts of potassium iodide in 500 parts of water is warmed to a temperature of about 35° C. under a nitrogen atmosphere. Then, 70.0 parts of potassium hydroxide is added. After further heating to about 55° C., 138.0 parts of 1,1-dimethoxy-1-(4-fluorophenyl)-4-chlorobutane is added. The temperature is then raised to about 102° C. and heating continued for 3.5 hours. After cooling to about 75° C., 785 parts of toluene is added to the reaction mixture and stirred for about 5 minutes. An additional 320 parts of toluene is added and the water and organic layers separated. 102 Parts of methanol is used to rinse the flask and added to the organic layer to provide a solution of 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4,4-dimethoxybutyl]-piperidin-4-ol. Then, 59 parts of concentrated hydrochloric acid is added to a stirred solution of the organic layer to precipitate a solid. The solid is filtered, rinsed twice with 550 parts by volume portions of a 10:9:1 acetone-toluene-methanol mixture, twice with 400 parts by volume portions of a 10:1 acetone-methanol mixture, and air-dried. The dried solid is then dissolved in 1950 parts of methanol with gentle heating on a steam bath. The resulting solution is filtered and 300 parts by volume of concentrated ammonium hydroxide is added. Heating is continued to reflux and maintained thereat for about 1 hour. Then, 2520 parts of water is added and the slurry stirred at about 75° C. for 1.5 hours. After cooling to about 25° C., the solid is filtered, washed twice with 600 parts by volume portions of a 3:1 mixture of water-methanol, and air-dried. The resulting product, 4-[4-chlorophenyl)-4-hydroxypiperidino]-4'-fluorobutyrophenone, is obtained in 32.5% yield. This product melts at about 148.5° - 150.5° C., and is represented by the following structural formula. ##STR8##

Workup

  1. temperatureThe temperature is then raised to about 102° C.
  2. temperatureheating
  3. temperatureAfter cooling to about 75° C.
  4. customthe water and organic layers separated
  5. washto rinse the flask
  6. additionadded to the organic layer

Sources & evidence

ORD record
ord-8bad22cf06f941c693c4856e7653917d
Source dataset
uspto-grants-1978_04
Patent number
US04086234

Reaction notes

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