Originator
Tindal ,Schering ,US ,1961
Manufacturing Process
The requisite intermediate, 10-(3-chloropropyl)-2-acetylphenothiazineis
prepared as follows: To a suspension of sodium amide (from 3 grams of
sodium) in 300 ml of liquid ammonia is added 30 grams of 2-
acetylphenothiazine. After stirring for one hour, there is added 19 grams of 1-
bromo-3-chloropropane. The ammonia is allowed to evaporate and the residue
is diluted with 200 ml of water. The mixture is extracted with ether and the
ether solution is dried over anhydrous sodium sulfate, filtered and
concentrated.
The residue consists of crude 10-(3-chloropropy1)-2-acetylphenothiazine as a
viscous oil and is used in the next step without further purification. The crude
base obtained from the reaction of 10-(3-chloropropyl)-2-acetylphenothiazine
with 1-(2-hydroxyethyl)piperazine is purified by conversion to its dimaleate
salt, MP 167-168.5°C from ethanol.
