close

Вход

Забыли?

вход по аккаунту

?

Патент USA US3077480

код для вставки
tates
atent
r.
31,077,470
W?
Patented‘ Feb. 12, 19753
1
In accordance with the invention‘ the new amine prod
3,677,470
ucts are prepared by the condensation of a phenol com
3{Li-HYDRGXY-S-(AMlN0h/[ETHYL)-PFillENYL]
pound having the formula,
4-(4-QXYPHENYD-ALKANES AND ALKENES
.ioseph H. l’iurclthalter, Ann Arbor, Mich” assignor to
gniversity of Kansas Research Foundation, Lawrence,
‘
ans.
and formaldehyde, and an amine having the formula,
No Drawing. Filed Mar. 21, 1961, Ser. No. 97,169
9 Claims. ((12. 260-—239)
HNR1R2
This invention relates to novel amine compounds and 10 where R1, R2, and Y have the above-mentioned signi?';
cance. The formaldehyde may be supplied as gaseous
means of obtaining the same. More particularly, the in
formaldehyde, aqueous formaldehyde or as formaldehyde '
vention relates to amine compounds which in free base
generating compounds such as paraformaldehyde. In
form have the general formula,
general, although the reaction can be run without‘ added l
15 solvent, preferably, it is carried out in an‘ inert solvent
such as benzene or in an alcoholic-type solvent as exam
ples of which may be mentioned methanol, ethanol, pro
panol, isopropanol and the like. The reaction proceeds
merely by adding the reactants together and allowing the
reaction mixture to stand at room temperature.
acid salts thereof and the corresponding quaternary low
er alkyl ammonium salts having the general formula,
As av
preferred mode of effecting‘the condensation, the reaction
mixture is heated at the boiling point ‘until the reaction
is substantially complete.
Ordinarily the reaction is com- -
plete within 2 to 3 hours at elevated temperature‘and at
25 lower temperature may require a longerrreaction time.=
The quaternary lower alkyl ammonium salts having the.
no-Q-Y-Q-ott
general formula indicated above are prepared in accord~
ance with the invention by reacting the‘ mentioned. aryl
where R represents hydrogen or a lower alkyl group
(i.e., an alkyl group containing from one to four car
ether having the general formula;
bon atoms, preferably methyl or ethyl), R1 and R2 inde
pendently represent lower alkyl groups (i.e., alkyl groups
, I
.
/Rl
CH2N\ R2
containing from 1 to 4 carbon atoms) or when taken to
gether with -—N represent a saturated heterocyclic radical
RWQFQIQOH
such as pyrrolidino, piperidino, piperazino, morpholino,
hexamethyleneimino and lower alkyl (i.e., l to 4 carbon 35
alkyl) substituted derivates thereof, the alkyl group be
with an equivalent amount of an alkyl ester‘having the .
ing substituted at the secondary nitrogen atom where
formula R3X such as an alkyl halide, sulfate or sulfonate; .
present or at one or more of the heterocyclic carbon
where R1, R2, R3, X and Y have the above-mentioned
atoms, X is an anion such as a chloride, bromide, iodide,
signi?cance. The reaction may be carried out over a
sulfate, or para-toluene sulfonate anion, R3 is a lower
wide range of temperature as. desired, e.g.,- at room tem
alkyl group (i.e., an alkyl group containing from 1 to 4
perature or higher temperature. The reaction with alkyl‘
carbon atoms) and Y represents a divalent hydrocarbon
bromides or iodides proceeds quite readily in. relatively
bridge containing not more than 3 carbon atoms option
short periods of‘ time, whereas the reaction with alkyl.
ally substituted with one or more lower aliphatic groups,
chlorides may require longer periods unless one employs .
an elevated ‘temperature. Conveniently, the reaction may
such as
be carried out by dissolving ‘the aryl ether starting ma~r
terial in an inert organic solvent. such as ether,‘ benzene
and the like, and by treating solution‘with‘the alkyl ester.
The resulting quaternary lower'alkyl ammonium com- -,
50
pound obtained in the reaction can be readily isolated by: ~
precipitation from solution brought about by the addition ‘_
of an organic solvent in which the product is insoluble
55
such as petroleum ether, and thelike. The ‘desired prod
uct, which separates, is then convenientlyrecovered as-by
?ltration, decantation, etc.
i.
The products of the invention possess signi?cant anti
bacterial properties and hence are useful as germicidal
ingredients or" soaps, detergents and the like. They are
particularly
useful ‘when administered?oralln as: agents
60
for‘ the lowering of the cholesterol level of the. blood‘.
The compounds of the instant invention‘possess little or,
no immediate estrogenic activity, thus making the com
As indicated, the invention contemplates products in
the free base form having the formula given above or in
salt form with an inorganic or organic acid. As exam
ples of the many acid salts contemplated by the invention
there may be mentioned the mineral acid salts such as
pounds particularly adaptable for administration in those
conditions where it is desired to lower the cholesterol
blood levels without causing the undesirable estrogenic
side eifects normally associated with the use of certain
anti-hypercholesterolemic substances.
The indicated
oral dosage is in general about 1-10 mg:/kg. daily. The
the hydrochloride, hydrobromide, hydroiodide, sulfate,
compounds are preferably administered in acid salt fornr
phosphate and the like, and organic acid salts such as the 70 which can be obtained from the corresponding free base:
citrate, tartrate, acetate, benzoate, phenylsul‘fonate, p
by dissolving the latter in a suitable solvent such as ether,
toluene sulfonate, sulfamate and like salts.
treating the solution with at least one equivalent of the
3
4
desired acid and recovering the solid product which sepa
rates from solution. The invention contemplates the
moved by ?ltration and recrystallized from a mixture of
alcohol and petroleum ether. The crystalline product is
mentioned acid addition salts and quaternary ammonium
salts broadly and includes such salts Whether non-toxic
or toxic since any salts of the invention which are con
sidered toxic are nevertheless useful as intermediates for
3-[4-hydroxy-3-(4 - morpholinylmethyl) - phenylj-4-(4
methoxyphenyl)-hexane hydrochloride, MP. 202° C.
Example 5
the production of non-toxic salts or the corresponding
A mixture of 0.3 g. of paraformaldehyde and 0.85 g.
free base, being readily convertible thereto by means
of piperidine is warmed with 25 ml. of absolute ethanol
which per so are known to those skilled in the art.
until a clear solution is formed. This solution is cooled
The invention is illustrated by the following examples. 10 to room temperature and added to 2.84 g. of hexestrol
monomethyl ether in 15 ml. of alcohol. The resulting
Example 1
mixture is allowed to stand at room temperature for one
A mixture of 2.84 g. of hexestrol monomethyl ether,
0.3 g. of paraformaldehyde and 0.71 g. of pyrrolidine
in 25 ml. of absolute ethanol is heated under re?ux on
a steam bath for two hours. The solvent is removed and
the residual product, 3-[4-hydroxy-3-(1-pyrrolidinyl
hour and then heated at re?ux temperature for 16 hours.
The alcohol is removed under reduced pressure and the
residual product, 3- [4-hydroxy-3- ( 1-piperidinylmethyl)
phenyl]-4-(4-methoxyphenyl)~hexane, is dissolved in 200
ml. of ether. Dry hydrogen chloride gas is passed into
methyl)-phenyl]-4-(4-methoxyphenyl) » hexane, is dis
the solution until it is saturated, the white solid is re
solved in ether. An excess of hydrogen chloride is added
moved by ?ltration and recrystallized from alcohol-petro
to the solution, the solid removed by ?ltration and re 20 leum ether. The crystalline product is 3-[4-hydroxy
crystallized from acetonitrile. The crystalline product is
3-(1-piperidinylmethyl) - phenyl]~4-(4-methoxyphenyl)—
3-[4-hydroxy-3-(l-pyrrolidinylmethyl)-phenyl] - 4 - (4
hexane hydrochloride, MP. 186° C. By substituting in
this procedure, for piperidine, an equivalent quantity of
Z-methylpiperidine one obtains, in crystalline form, the
methoxyphenyl)-hexane hydrochloride, Ml’. 183-1845o
C.
Example 2
corresponding product, 3 - [4 - hydroxy-3-(N-2-methyl
piperidinylmetliyl) - phenyH-d-(4-nethoxyphenyl) - hex
A mixture of 0.3 g. of paraformaldehyde and 1.6 ml.
of 30% ethanolic 'dimethylamine in 25 ml. of absolute
ethanol is warmed until a clear solution is formed. This
stituting an equivalent quantity of hexamethyleneimine
solution is cooled to room temperature and added to
one obtains 3 - [4-hydroxy-3-(1 - hexamethyleneiminyl
ane hydrochloride, MP. l95—200° C. Likewise, by sub
2.84 g. of hexestrol monomethyl ether in 15 ml. of abso~ 30 methyl)-phenyl]-4-(4-rnethonyphenyl) - hexane hydro
chloride, Ml’. 202~210° C.
lute ethanol. The resulting mixture is allowed to stand
at room temperature for one hour and then heated at re
Example 6
flux for 16 hours. The alcohol is removed under reduced
pressure and the residual product, 3-(4-hydroxy-3-di
.84 g. of hexestrol monomethyl ether, 1.1 g. of l
methylpiperazine and 0.33 g. of paraiormaldehyde in
methylarninomethylphenyl)-4-(4-methoxyphenyl) - hex~
25 ml. of absolute ethanol is heated on a steam bath for
ane, is dissolved in ether. Dry hydrogen chloride gas is
passed into the solution until it is saturated. Additional
other is added and the white precipitate is removed by
two hours. The solvent is removed and the residual
product, 3- [4~hydroxy-3-( 1~methyl-4-piperazinylrnethyl) -
phenyl]~4-(4-methoxyphenyl)hexane, is dissolved in 50
ml. of ether. Dry hydrogen chloride gas is added until
ethyl acetate. This product is 3-(4-hydroxy-3-dimethyl 40 saturation and the white precipitate is removed by ?l
aminomethylphenyl)-4-(4-methoxyphenyl) - hexane hy
tration and recrystallized from alcohol. The crystalline
drochloride, MP. 181° C.
product is 3-[4-hydroxy-3-(l~methyl-4-piperazinylmeth
yl) - phenyl] - 4 - (4 - methoxyphenyl) - hexane di
Example 3
hydrochloride monohydrate, Mi’. 249-251” C. (doc).
A mixture of 0.3 g. of paraformaldehyde and 0.8 g. 45
Example 7
of diethylamine is warmed with 25 ml. of absolute ethanol
until a clear solution is formed. This solution is cooled
An alcoholic mixture of 13.4 g. of diethylstilbestrol,
to room temperature and added to 15 ml. of absolute
1.5 g. of paraformaldehyde and 3.8 g. of diethylamine
ethanol containing 2.84 g. of hexestrol monomethyl ether.
is heated at re?ux temperature for two hours. The sol
?ltration and recrystallized from a mixture of acetone and
The resulting mixture is allowed to stand at room tem
perature for one hour and then heated at reflux for 16
hours. The alcohol is removed under reduced pressure
vent is removed under reduced pressure and the residue
is dissolved in 50 ml. of ether. The ethereal solution
is extracted three times with 5% potassium hydroxide so
and the residual product, 3-(4-hydroxy-3-diethylamino
lution. The alkaline extract is neutralized with dilute
methylphenyl)~4-(4-methoxyphenyl)~hexane, dissolved in
acetic acid, to give a solid which is extracted with ether,
ether. Dry hydrogen chloride gas is passed into the solu 55 and dried over anhydrous sodium sulfate. The drying
tion-until it is saturated and the white precipitate re
agent is removed and the ethereal solution is saturated‘;
moved by ?ltration and recrystallized ?rst from alcohol
with hydrogen chloride. The solid is collected by ?ltra
and petroleum ether (1:1), and then from acetone and
tion, dissolved in 25 ml. of hot water and neutralized with
petroleum ether (1:1). The product is 3-(4-hydroxy-3
diethylaminomethylphenyl)-4-(4-methoxyphenyl) - hex
ane hydrochloride, MP. 166.5° C.
Example 4
dilute ammonia. The product, 3-(4-hydroxyphenyD-4
60 (4-hydroxy-3-diethylaminomethylphenyl)~3-hexene, is re
moved by ?ltration and puri?ed by recrystallization from
dilute ethanol; MP. 135-136“ C.
Example 8
A mixture of 0.3 g. of paraformaldehyde and 0.9 g.
of morpholine is warmed in 25 ml. of absolute ethanol 65
Into 25 ml. of absolute ethanol is placed 0.3 g. of para
until a clear solution is formed. The solution is cooled
formaldehyde and 1.6 ml. of 30% ethanolic dimethyl~
to room temperature and added to 15 ml. of alcoholic
amine. This mixture is gently heated until a clear solu
solution of 2.84 g. of hexestrol monomethyl ether. The
tion is formed and then cooled to room temperature. A
resulting mixture is allowed to stand at room tempera
solution of 2.82 g. of diethylstilbestrol monomethyl ether
ture for one hour and then heated at re?ux temperatures 70 in 10 ml. of absolute ethanol is added. After standing
for 16 hours. The alcohol is removed under reduced
at room temperature for one hour, it is heated at reflux
pressure and the product, 3-[4-hydroxy-3-(4-morpholinyl
temperature for 10 hours, and the alcohol is removed by
methyl)-phenyl]-4-(4-methoxyphenyl) - hexane, is dis
distillation in vacuo. The residual product, 3-(4-meth
solved in ether. Dry hydrogen chloride gas is passed into
oxyphenyl) - 4 - (4 ~ hydroxy - 3 - dimethylamiuometh
the solution until it is saturated, and the white solid re
yl-phenyD-3-hexene, is dissolved in ether and the ethereal
-s,077,470
5
solution is saturated with hydrogen chloride gas. The
resulting precipitate is isolated by ?ltration and recrys:
tallized from a mixture of alcohol and petroleum ether.
it
ride and the gummy precipitate which forms is triturated
with a spatula until it becomes a white solid and is then
recrystallized from a mixture of alcohol and petroleum
The crystalline product is 3-(4-methoxyphenyl)~4-(4-hy
ether to give 3-[4-hydroxy-3~(l-piperidinylrnethyl)-phen
droxy - 3 - dimethylaminomethylphenyl) - 3 - hexene
yl] - 4 - (4 - methoxyphenyl) - 3 - hexene hydrochloride,
hydrochloride, MP. 203.5° C. By substituting in this
procedure an equivalent amount of diethylarnine for di~
methylamine, one obtains the corresponding product, 3
MP. 178° C. By substituting for piperidine an equiv
alent quantity of hexamethyleneimine in this procedure,
one obtains the corresponding product, 3-[4-hydroxy-3
(4 - methoxyphenyl) - 4 - (4 - hydroxy - 3 - diethyl
aminomethyl-phenyl)-3-hexene hydrochloride, M.P. 180
182° C.
(l - hexamethyleneiminylmethyl)
10 methoxyphenyl)-3-hexene
- phenyl] - 4 - (4
hydrochloride, M1’.
200° c.
Example 9
Into 25 ml. of absolute ethanol is placed 0.3 g. of para
formaldehyde and 0.9 g. of morpholine. This mixture
is gently heated until a clear solution is formed and is then
cooled to room temperature whereupon a solution of 2.82
g. of diethylstilbestrol monomethyl ether in 10 ml. of
absolute ethanol is added. After standing at room tem
perature for one hour, the mixture is heated at re?ux
temperature for 10 hours and then the alcohol is re
moved in vacuo. The residual product, 3-(4-rnethoxy
phenyl) - 4 - [4 - hydroxy - 3 - (4 - morpholinylmethyl)
195‘
Example 13
1(a) An alcoholic mixture of 14.9 g. of 3-ethy1-2,4-bis~
(ll-hydroxyphenyl)hexane, 1.5 g. of paraformaldehyde
and 3.8 g. of diethylamine in 100 ml. of ethanol is heated
at reflux temperature for two hours. The solvent is re
moved by distillation in vacuo and the residue is dissolved
in ether. The ether solution is extracted three times with
5% potassium hydroxide solution. The alkaline extract
is neutralized with dilute aqueous acetic acid to give a
solid which is extracted with ether and the ethereal solu
tion is dried over sodium sulfate. After removing the
phenyl]~3-hexene, is dissolved in ether and the ethereal
solution saturated with hydrogen chloride gas. The gum
my precipitate is removed by ?ltration and recrystallized
tralized with dilute ammonia. The product, 3-ethyl-4-(4
from a mixture of acetone alcohol and petroleum ether.
hydroxyphenyl) - 2 - (4 - hydroxy - 3 - diethylarninometh
drying agent, the ether solution is saturated with hydro
gen chloride. The solid is dissolved in hot water and neu
The product is 3-(4-rnethoxyphenyl)-4-[4-hydroxy-3-(4
ylphenyl)-hexane, is removed by ?ltration and puri?ed
morpholinylmethyl) ~ phenyl] - 3 ~ hexene hydrochlo
by recrystallization from dilute ethanol, M.P.. 135~l36° C.
ride, lvLP. 183° C.
(b) The product of (a) is dissolved in ether and the
30
Example 10
ethereal solution treated with an excess oi dry gaseous
hydrogen bromide. The hydrobrornide salt which sep~
Into 25 ml. of absolute ethanol is placed 0.3 g. of
arates from the solution is collected and puri?ed by re
paraformaldehyde and 0.71 g. of pyrrolidine. This mix
crystallization
from isopropanol. Likewise, the tartrate
ture is gently heated until a clear solution is formed and
is then cooled to room temperature. A solution of 2.82 35 salt can be prepared by adding such an ether solution to
isopropanol solution containing an equivalent amount‘
g. of diethylstilbestrol monomethyl ether in 10 ml. of
of tartaric acid and recovery of the solid tartrate salt
absolute ethanol is added to the previous mixture. After
which separates on standing.
standing at room temperature for one hour, it is heated
Example 14
at re?ux temperature for 10 hours. The alcohol is re
moved in vacuo, the residue dissolved in ether and the 40
0.6 ‘g. of paraformaldehyde is added to 12 g. of diethyl
ethereal solution saturated with hydrogen chloride gas.
amine and the mixture is gently warmed to produce a
The gummy precipitate which forms is removed by lil
solution. 5.4 g. of hexestrol is added and the reaction
tration and decantation and recrystallized from a mixture
mixture is refluxed 'for three hours and the excess amine
of acetone, alcohol and petroleum ether to give 3-(4
is removed by distillation in vacuo. The residue is taken
methoxyphenyl) - 4 - [4 - hydroxy - 3 - (l - pyrrolidinyl
methy1)-pheny1]-3-hexene hydrochloride; MP. 190° C.
Example 1]
Into 25. ml. of absolute. ethanol is. placed 0.3 g. of
para'iormaldehyde and 1.0 g. of l-methylpiperazine. The
mixture is gently heated until a clear solution is formed
and is then cooled to room temperature.
A solution of
2.82 g. of diethylstilbestrol monomethyl ether in 10 ml.
01' ethanol is added. After standing at room tempera
ture i‘or one hour, it is heated at re?ux temperature for
' 10 hours.
The alcohol is removed by distillation in
vacuo and the residue dissolved in ether. The ethereal
solution is saturated with hydrogen chloride gas and the
up in 25 ml. of methanol and placed at 0 to 5° C. for 16
hours. The white precipitate is removed by ?ltration and‘
the ?ltrate evaporated to dryness. The residual oil is
taken up in ether‘and saturated with hydrogen chloride.
The precipitate is removed and triturated with acetone.
It is further triturated with cold water to give a relatively
pure hydrochloride salt which on recrystallization from
ethanol, acetone and ether gives 3-(4-hydroxyphenyl)-4
(4 - hydroxyphenyl - 3 - diethylaminomethylphenyl) - hex
ane hydrochloride, M. P. 226-226.5° C.
The hydrochloride is taken up in water and treated with
sodium carbonate. The precipitate is removed and re
crystallized from benzene and petroleum ether. The
product is 3-(4-hydroxyphenyl)~4-(4-hydroxyphenyl-3-di
gummy precipitate which forms is removed and recrystal
ethylaminomethylphenyl)—hexane, M.P. 130-131° C.
lized from alcohol and from alcohol and petroleum ether 60
to give 3 - (4 - methoxyphenyl) - 4 - [4 - hydroxy - 3
(1 - methyl - 4 - piperazinylrnethyl) - phenyl] - 3 - hexene
dihydrochloride, MP. 187.5° C.
Example 12
Into 25 ml. of absolute alcohol is placed 0.3 g. of
paratormaldehyde and 0.9 g. of piperidine. The reaction
Example 15
A mixture of 2.8 g. of dienestrol monomethyl ether
(M.P. 142°), 0.3 g. of paraformaldehyde and 0.71 g. of
pyrrolidine in 25 ml. of absolute ethanol is heated at re
?ux temperature for two hours. The solvent is removed
in vacuo, the residue dissolved in ether and the ethereal
solution saturated with hydrogen chloride gas.
The
mixture is gently heated until a clear solution is formed
gummy precipitate, after decantation of solvent, is tri—
and is then cooled to room temperature. A solution of
with acetone. The resulting solid product is 3
2.82 g. of diethylstilbestrol monomethyl ether in 10 ml. 70 turated
(4- - methoxyphenyl) - 4 - [4 - hydroxy - 3 - (1 - pyrroli~
of alcohol is added to the above mixture. After stand
dinylmethyl ) ~phenyl] -2,4-hexadiene hydrochloride.
ing at room temperature for one hour it is heated at re
Example 16
?ux temperature for 10 hours. The alcohol is removed
by distillation in vacuo and the residue dissolved in ether.
A mixture of 3.3 g. of benzestrol monoethyl ether, 0.3
The ethereal solution is saturated with hydrogen chlo 75 g. of paraformaldehyde and 1.0 g. of l-methylpiperazine
dorm-r0
8
in 30 ml. of ethanol is heated under re?ux for three
hours. Excess hydrogen chloride is passed into the solu~
tion and the solvent removed. The residual product, 3
I claim:
1. A member of the group consisting of a free base,
acid addition salts thereof and the corresponding quater
nary lower alkylammonium salts wherein the anion is a
member selected from the group consisting of chloride,
ethyl ~ 2 - (4 ~ ethoxyphenyl) - 4 - [4 ~ hydroxy - 3 - (1
methyl - 4 - piperazinylmethyl) - phenyl] a hexane
dihy
drochloride, can be puri?ed if desired by recrystallization
bromide, iodide, sulfate and para-toluene sulfonate, said
from alcohol-petroleum ether mixture. The starting ma
free base having the formula,
terial, benzestrol monoethyl ether, can be prepared by
the procedure of Wilds et al., J.A.C.S., 70, 4128 (1948),
for the monomethyl ether wherein dimethyl sulfate is re 10
placed with diethyl sulfate.
Example 17
The residual product, 3-(4-hydroxy-3-dimethylamino
methylphenyl)~4-(4-methoxyphenyl)~hexane, obtained in
where R is a member of the group consisting of hydro
gen and lower alkyl; R1 and R2 independently represent a
accordance with the procedure of Example 2 is dissolved
in 3.5 ml. of benzene. The solvent is removed by dis
tillation until the distillate is clear, and then a constant
stream of methyl chloride gas is bubbled through the solu
tion for over a half hour.
member selected from the group consisting of lower alkyl
and further members wherein R1 and R3 taken together
with
After standing for a few 20
N
hours at room temperature, the resulting precipitate is
collected by ?ltration. The product, 3-(4-hydroxy-3-di
represent a heterocyclic radical of the group consisting of
methylaminomethylphenyl) - 4 - (4 - methoxyphenyl)
pyrrolidino, piperidino, piperazino, morpholino, hexa
hexane methochloride, is purified by recrystallization from
methyleneimino and lower alkyl substituted derivatives
thereof; and Y is a member of the group consisting of
ace-tonitrile; MP. 223-224“ C.
Example 18
3 - (4 - methoxyphenyl) — 4 - [4 - hydroxy - 3 - (1 - py1"—
rolidinylmethyl)-phenyl]-3-hexene hydrochloride (1 g.)
is taken up in water and treated with excess in aqueous
2. 3 - [4 - hydroxy - 3 - (l - pyrrolidinylmethyl) - phen
ammonia. The resulting mixture is extracted with three
25-1111. volumes of ether, the ether extracts combined and
yl] -4- ( 4-methoxyphenyl ) -hexane hydrochloride.
dried over anhydrous sodium sulfate. The dried extracts
yl) -phenyl] -4- ( 4-methoxyphenyl ) hexane hydrochloride.
3. 3 - [4 - hydroxy - 3 - (N - 2 - methylpiperidinylmeth
are ?ltered, an excess of methyl iodide is added to the
?ltrate, and the mixture is allowed to stand for several
hours at room temperature. The product, 3-(4-methoxY
4. 3 - (4 - hydro-xy - 3 - diethylaminomethylphenyl) - 4
(4-rnethoxyphenyl)-hexane hydrochloride.
5. 3 - [4 - hydroxy - 3 - (l - piperidinylmethyl) - phen
yl]-4-(4-methoxyphenyl)—3-hexene hydrochloride.
phenyl) - 4 - [4 - hydroxy - 3 - (l - pyrrolidinylmethyl)»
phenyl1-3-hexene methoiodide, is collected by ?ltration.
Example 19
2 g. of 3-(4-hydroxyphenyl)-4-(4-hydroxy-3-diethyl
6. 3 - [4 - hydroxy - 3 - (l - piperidinylmethyl) - phen
yl] -4- ( 4-rnethoxy-phenyl) hexane hydrochloride.
40
'7. 3 - (4 - methoxyphenyl) - 4 - (4 - hydroxy - 3 - di
methylaminomethylphenyl) ~3-hexene hydrochloride.
aminornethylphenyl)hexane, Ml’. 130-13l° C., is dis
8. 3 - [4 - hydroxy - 3 - (1 - hexamethyleneiminylrneth
solved in 25 m1. of alcohol and an excess of ethyl iodide
yl) -phenyl]~4-(4-methoxyphenyl)hexane hydrochloride.
is added. After standing for two hours, the solvent is
9. 3 - [4 - hydroxy - 3 - (4 - morpholinylmethyl)
removed and the residue recrystallized from alcohol and 45 yl]-4-(4~rnethoxyphenyl)hexane hydrochloride.
acetonitrile to give 3-(4-hydroxyphenyl)-4-(4-hydroxy-3
diethylaminomethylphenyl)-hexane ethoiodide.
References Cited in the ?le of this patent
This application is a continuation-in-part of my copend
UNITED STATES PATENTS
ing application Serial No. 746,670 ?led July 7, 195 8, now
abandoned.
50
2,260,967
- phen
Bruson ______________ __ Oct. 28, 1941
Документ
Категория
Без категории
Просмотров
0
Размер файла
677 Кб
Теги
1/--страниц
Пожаловаться на содержимое документа