Potassium Iodide → Haloperidol hydrochloride

HRID 2083662Notes

Reaction equation

HRID 2083662 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:14])[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[I-].[K+].C(=O)(O)[O-].[K+].C[O:23][C:24](OC)([C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=1)[CH2:25][CH2:26][CH2:27]Cl>C1(C)C=CC=CC=1.O>[ClH:1].[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:14])[CH2:9][CH2:10][N:11]([CH2:27][CH2:26][CH2:25][C:24]([C:29]3[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=3)=[O:23])[CH2:12][CH2:13]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 382824-(4-Chlorophenyl)-4-hydroxypiperidineHCID 516893Potassium BicarbonateHCID 112766731-(4-CHLORO-1,1-DIMETHOXYBUTYL)-4-FLUOROBENZENE

Product 1

HCID 11495267Haloperidol hydrochlorideYield 80.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

4.87 Parts of 4-(4-chlorophenyl)piperidin-4-ol, 1.91 parts of potassium iodide and 25 parts of deionized water is stirred together and gently warmed under a nitrogen atmosphere. Then, 2.75 parts of potassium bicarbonate and 6.17 parts of 1,1-dimethoxy-1-(4-fluorophenyl)-4-chlorobutane is added and the mixture is heated to reflux. After heating for 4.5 hours, the reaction mixture is allowed to cool to room temperature and 55 parts of toluene is added. The aqueous and organic layers are separated, and the aqueous layer discarded. 5.1 Parts of methanol is added to the organic layer. Then, 2.5 parts of concentrated hydrochloric acid is added with vigorous stirring. The resulting precipitate is cooled to about 25° C., filtered, washed twice with 22 parts by volume portions of a 10:9:1 mixture of acetone-toluene-methanol, and twice with 20 parts by volume portions of a 10:1 mixture of acetone-methanol. After air-drying, the product, 4-[4-(4-chlorophenyl)-4-hydroxypiperidino]-4' -fluorobutyrophenone hydrochloride, melts at about 227°-229° C. and is obtained in 80.1% yield. This compound is the hydrochloride salt of the product of Example 1.

Workup

  1. temperaturegently warmed under a nitrogen atmosphere
  2. temperaturethe mixture is heated to reflux
  3. temperatureAfter heating for 4.5 hours
  4. customThe aqueous and organic layers are separated
  5. addition5.1 Parts of methanol is added to the organic layer
  6. additionThen, 2.5 parts of concentrated hydrochloric acid is added with vigorous stirring
  7. temperatureThe resulting precipitate is cooled to about 25° C.
  8. filtrationfiltered
  9. washwashed twice with 22 parts by volume portions of a 10:9:1 mixture of acetone-toluene-methanol
  10. additiontwice with 20 parts by volume portions of a 10:1 mixture of acetone-methanol
  11. customAfter air-drying

Sources & evidence

ORD record
ord-2267b15d291041969fe3fc8d510ab769
Source dataset
uspto-grants-1978_04
Patent number
US04086234

Reaction notes

Loading…