5.23 g of phenothiazine-10-carboxylic acid chloride were suspended in 8 g of
dimethylaminoethoxyethanol and heated, with stirring, under anhydrous
conditions, first for 1 hour at a temperature of 50°-105°C, then for another
hour at 108°-110°C. All the suspended acid chloride had dissolved after the
final heating, and the solution was then allowed to cool slowly to 75°C over a
period of one hour. Infrared examination of a sample showed that the
esterification reaction was essentially complete after the second hour
The reaction mixture was then poured on 1 liter of crushed ice, and the oily
precipitate washed repeatedly by decantation with ice water. It was then taken
up in 75 ml of benzene, and again washed repeatedly with water until a pH of
8.2 in the washings indicated that substantially all of the excess β-
dimethylaminoethoxyethanol had been removed. The benzene solution was
then dried with anhydrous sodium sulfate, filtered, and the benzene
evaporated in a current of dry nitrogen gas. The residual dark oil constituted
the desired basic ester. β-Dimethylaminoethoxyethyl phenothiazine-10-
carboxylate.
The basic ester may be dissolved in anhydrous ether and then precipitated by
adding a slight excess of a solution of dry hydrogen chloride in ether and the
hydrochloride salt may be isolated as an amorphous, glasslike product, which
could be crystallized from anhydrous acetone or from methanol-ether. In this
manner there was obtained as a stable, crystalline, colorless substance β-
dimethylaminoethoxyethyl phenothiazine-10-carboxylate hydrochloride, one
sample of which melted at 161°-163°C with decomposition.
