Potassium Iodide → Haloperidol hydrochloride

Participants

Reaction Steps

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.

Provenance & Evidence