close

Вход

Забыли?

вход по аккаунту

?

Патент USA US3086032

код для вставки
United States Patent O?lice
3,086,022
Patented Apr. 16, 1963
1
2
3,086,022
by catalytic hydrogenation. Dehydration is ef
1,4-BIS(POLYALKYL
SUBSTITUTED-4-HYDROXY
4-PIPERIDYL) BUTANES
boiling in 20 percent sulfuric acid. Hydrogena
Robert I. Meltzer, Rockaway, and Wilson B. Lutz, Flor
ham Park, N.J., assignors to Warner-Lambert Pharma
ceutical
Company, Morris Plains, N.J., a corporation
of
Delaware
5
N0 Drawing. Filed Sept. 25, 1961, Ser. No. 140,214
3 Claims. (Cl. 260-~294.7)
those of such acids
The present invention relates to new and novel piper 10
idine derivatives having the formula
ylsulfonic, p-toluenesulfonic, sulfonic, sulfuric, phos
p oric, cinnamic, hydrochloric, hydrobromic
\
H30
on,
11.0’
N
H30
toluenesulfonate and
For therapeutic use, our new and novel compounds,
either as. the free base or in the form of a salt, may be.
\ If/<on.
R:
,
lit:
15
011,
R,
formulated with a conventional pharmaceutical carrier
to form tablets,
20 suppositories
R2
is
hydrogen
or
and capsules,
the like. elixirs, solutions, suspensions,
methyl and R3 is hydrogen or lower
pharmaceutically acceptable HOIIJtOXiC alkyl, and to the
The following examples are included in order further
wherein R1 is hydrogen or hydroxyl,
acid' addition and
quaternary ammonium salts thereof.
to illustrate our invention:
e compounds of our invention having the above
formula have been found to possess signi?cant pharma 25
,
a
-
EXAMPLE 1
1,4-Bz's (2,2,6,6-Tetramethyl-4-Hydr0xy-4
I
other piperidine
Piperidyl)Butane
1,4-bis(2,2,6,6-tetramethyl~4-hydroxy - 4 - piperidyD
We have now found that those compounds of our in
vention having the formula
1130
>
30
35
R2
If
R,
R3
I
Evaporation of the solvent gives
011,
R3
crude material which is recrystallized from 90-97° pe
troleum
128430“.ether to give 1.8 g. (97%) of white needles M.P.
in which R2 and R3 are as described hereinabove may be
prepared by the catalytic hydrogenation of compounds of 40 An additional recrystallization from
the formula
petroleum ether
followed by sublimation of
gives analytical
ly pure material, M.P. 128-l29°.
HO CEO-‘GEO on
\/
/
me
n30
Analysz's._Calc.: C, 71.68; H, 12.03; N, 7.60.
Found: C, 71.67; H, 12.14; N, 7.62.
on, mo
/-
If
<
R3
R.
R. N
1L3
<
which are described and claimed in our application Serial
'
1,4-Bis(1,2,2,6,6-Pentamethyl-4-Hydr0xy-4
Piperidyl)Butane
A mixture of 7.37 g. (0.02 mole) of 1,4-bis(2,2,6,6
50 tetramethyl-4-hydroxy
- 4 - piperidyl)butane, 32 ml.
37%
constitute useful cat
that those compounds of our in
55
M.P. 120-122".
An analytical sample, M.P. 1224123“ is obtained by
recrystallizing
similar material twice from ligroin and
subliming
the product.
vention having lower alkyl substituents on the piperidine
‘
prepared from the corresponding
compounds having hydrogen substituents on the nitrogen
atomsiby conventional alkyla-tion techniques.
Those compounds of our invention having the formula 60
'
CHz-OHz-GHz-CH;
“QUE “(lam
11.0
If
Ra
EXAMPLE 2
on.
No. 140,213, ?led September 25, 1961 entitled “Piper
idine Derivatives,” ?led concurrently herewith. Palladi
'
45
on.
\
R:
R. If
Analysis.—Calc.: C, 72.67; H, 12.20; N, 7.06. Found:
C, 72.59; H, 12.22; N, 7.01.
EXAMPLE 3
65
on.
Ra
may be prepared from the corresponding compounds hav
ing hydroxyl substituents at the 4 positions of the piper 70
idine rings by the steps of dehydration to form a diene
1,4-Bis(J,2,2,6,6-Pentametkyl-4-Piperidyl) Butane
A quantity of 9.2 g. of 1,4-bis(1,2,2,6,6-pentamethyl-4
hydroxy-4-p1per1dyl) butane is re?uxed for 61/2 hours in
3,086,022
3
of potassium sulfate. The ?lter cake is treated with a
little dilute hydrochloric acid and the inorganic material
removed by ?ltration. The ?ltrate is basi?ed and the
product extracted into ether. Evaporat'on of the dried
ether solution yields 8.3 g. of a crude product MP. 115-
116°, which reacts rather rapidly with potassium per
manganate in acetone indicating incomplete hydrogena
A.
is given merely by way of illustration and that many
variations may be made therein without departing from
the spirit of our invention.
we desire to se
Having described our invention what
cure by Letters Patent is:
1. A member selected from the group consisting of
compounds of the formula
tion. Recrystallization from methanol raises the M.P. to
116-1117°. However, a potassium permanganate test for
unsaturation is still positive. An additional recrystalli 10
zation raises the M1’. to 118.6~119.4°. Infrared analysis
> /<
\ /\
1130 If R;
R: If ‘on;
indicates the absence of hydroxyl groups; hence the prob
R3
R3
able impurity is assumed to be ole?nic material rather
group consist
than undehydrated substances.
15 wherein R2 is a member selected fromis the
a member of the
The remaining material is then subjected to high pres
group consisting of hydrogen and lower alkyl, and the
sure hydrogenation in 25% acetic acid at 1800-1900
p.s.i. over a mixture of platinum and palladium on char
non-toxic pharmaceutically acceptable acid addition salts
coal. Upon basi?cation of the ?ltered solution the prod
HZC q CH: 1130
LCHa
4 - hydroxy - 4 - piper
uct crystallizes. After recrystallization from methanol it 20 thereof.
2. 1,4-bis(2,2,6,6-tetrarnethyl melts at 120-121". Treatment with gaseous hydrogen
idyl)butane.
chloride in ether yields a dihydrochloride salt, MP. 276
3. 1,4-bis(1,2,2,6,6-pentamethyl-4-hydroxy - 4 - piper
277°. One recrystallization from ethanol-ethyl acetate
idyl)butane.
and four recrystallizations from Z-propanol yield 2.5 g.
(25%) of the puri?ed dihydrochloride of 1,4-bis(1,2,2,
25
References Cited in the ?le of this patent
6,6 - pentamethyl - 4 - piperidyl)butane, M.P. 289-290D
UNITED STATES PATENTS
N, 6.40.
2,624,735
Goldberg et al. ________ __ Jan. 6, 1953
Found: C, 65.60; H, 11.46; N, 6.70.
In the foregoing examples, all temperatures are given
in degrees centigrade.
It is understood that the foregoing detailed description
103,541
Great Britain __________ __ Feb. 1, 1917
(dcc.).
Analysis-Cale: C, 65.87; H, 11.52;
FOREIGN PATENTS
Документ
Категория
Без категории
Просмотров
0
Размер файла
199 Кб
Теги
1/--страниц
Пожаловаться на содержимое документа