Originator
Fenistil,Zyma,W. Germany,1961
Manufacturing Process
26 grams of 2-ethylpyridine is added dropwise with cooling to 20°C and in an
atmosphere of nitrogen to a stirred solution of 650 ml of an 0.37 molar
solution of phenyl lithium in benzene. After two hours a solution of 10 grams
of 2-(2-dimethylaminoethyl)-indan-1-one in 50 ml of dry ether is added over
a period of five minutes while stirring and cooling to room temperature. After
standing for 24 hours the organo-lithium compounds are decomposed by the
addition of 50 ml of water with external cooling. After separating the water
phase from the organic solution, the latter is washed several times with 50 ml
of water, and then extracted with a mixture of 40 ml of concentrated
hydrochloric acid and 100 ml of water.
The acidic solution, containing the 2-(2-dimethylaminoethyl)-1-[1-(2-pyridyl)-
ethyl]-indan-1-ol is heated on the steam bath for thirty minutes to effect
dehydration to the desired indene derivative. The solution is cooled, made
strongly basic with an aqueous solution of ammonia and then extracted with
ether. The ether phase is dried over sodium sulfate, filtered, evaporated and
the residue distilled.
At 15 mm pressure the excess of 2-ethylpyridine is removed, at 120°C/0.5
mm some unreacted 2-(2-dimethylaminoethyl)-indene distills and at 165°-
175°C/0.5 mm the 2-(2-dimethylaminoethyl)-3-[1-(2-pyridyl)-ethyl]-indene is
collected. It may be converted to an aqueous solution of the dihydrochloride
by dissolving it in the appropriate amount of dilute hydrochloric acid.
To a solution of 1.0 gram of 2-(2-dimethylaminoethyl)-3[1-(2-pyridyl)-ethyl]-
indene in 10 ml of ethanol is added while stirring and heating 0.4 gram of
maleic acid. On cooling the 2-(2-dimethylaminoethyl)-3-[1-(2-pyridyl)-ethyl]-
indene maleate crystallizes, is filtered off, washed with a small amount of
ethanol and recrystallized from ethanol, MP 158°C.
Synthesis
Benzylmalonic acid is esterified
with dihydropyran and reacted with sodium
hydride and 2-dimethylaminoethyl chloride in
toluene to give ditetrahydropyranyl-2-benzyl-2-
(2-dimethylaminoethyl)malonate, which is cyclized
with the help of polyphosphoric acid
to 2-(2-dimethylaminoethyl)-indan-1-one. This
compound reacts with 2-ethylpyridine and phenyllithium
to give the carbinol, which is dehydrated
by heating to dimetindene .
