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Патент USA US3074989

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United States Patent 0
M
._
lC€
a
3,074,978
Patented Jan. 22, 1963
2
1
wherein R is an alkyl radical having 1 to 18 carbon atoms
3074 978
PROCESS FGR THE 9 PR’EI’ARATKQN OF 135-11
and Ac‘is the acyl radical of an organic carboxylic acid
having 1 to 18 carbon atoms. .
PR?i’YL-A‘l-GONENE=17B=OL-3-ONE AND THE
The oarboxylic acid esters of the 13?~alkyl-A4-gonene
INTERMEDIATES IN THE PREPARATION
THEREGF
B
5 17B-ol-3-ones are more fully described in the copending,
Gerard Nomi“, Noisy-165% (Seine), and R?belft 11commonly assigned US. application Serial No. 96,062
court, Villiers-le-Bel (Seine and Oise), France, assignors
iaaggélssel‘ucLAFr PM“, France’ a c0rl'm'i‘tml 0f
.
,
acids having 1 to 18 carbon atoms may be alkanoic or
’légagggvg?ghg'gggiigh?nl?ihgirjgoi1i61%?
5 C]a?ims_ (CL 260__397_4)'
.
?led January 19, 1961_ The 135-2,1ky1 radical is an alkyl
radical having 1 to 18 carbon atoms. The carboxylic
10 alkenoic acids, cycloalkyl alkanoic acids, aryl alkanoic
’
acids or aryl carboxylic acids as set forth in said co
.
,
pending application.
The invention relates to a novel method for the saponi?cation of carboxylic acid esters -of_13;8-_alk_yl-A -gonene-
-
The carboxylic ,acid esters of the 13 ?dalkybA4_gonene_
17B_o1_3_one may be prepared according to the process
17/8-ol-3-ones wherein the carboxylic acid is an organlc 15 disclosed in United States ‘Patent application Serial No.
WWW“ and having 1 to 1.8 who‘? atoms‘ The .mven'
tron also ‘relates to novel intermediates ‘formed in the
96,062 and is illustrated by the steps comprising reacting
an anyl halide with 6_methoxy_3AdihYdmnaPhthYl‘Q,1)_
Sa?°m?cat1_°n PIPCCSS' Tile direct saPom?ca’uon of, "the
isoxazole followed by hydrogenation to form 2-cyano-2-n
said esters is particularly di?icult and gives only mediocre
Weld?‘
_
_
.
_
PYOPYL6_methoxy_tetralone_1, reacting the latter with di_
20 methyl
It IS an obiect of the invention to provide a novel process for ‘the sapom?cation of carboxylic acid esters of 1318alkylfA 'gonene‘ll?'om'onesj m 111511 welds‘ ,
_
succinate to form 5-methoxy-13B-n-propyl-l5
mathoxycarbony1_A5,q,9,14_des A_gonat6traene_17_one’ I?’
acting the latter with an alkali metal borohydride to form
5 - methoxy-13?-n-propyl-l5-carboxy-A5Y'L9J4-des A-gona
It '15 lanother object of the “.wentlon ‘to obt'éim “9W1 111'
tetraeneal7B-ol, heating the latter under acid conditions to
termnediates for; the saponi?cation of carboxyhc acid esters 25 form 5_methoXy_13B_n_pmpy1_A5,q,9,14_des A_gonatetmene_
of l’?'alkyl'A "gOHeQe‘U?‘OI‘B'OHeS and Pamculaxly:
175-01, reducing the latter to form 5-methoxy-l3?-n-pro
(a) The lJEIIZOIC 361d ester ‘of 13/3*11*P1"°PY1-A4*g0ne11e~
pyl-A517,9~des-A-gonatriene-l7?-ol, reacting the latter with
3,17?-di01
sodium in ammonia to form 13?~n-propy1-A9-des A-go
(b) l3?rn-pfopyl-A4-gonene-3,17?-di01.
nene-l’i'B-ol-S-one, esterifying the latter with benzoic acid
These and other objects and advantages of the invention 30 to form l3?-n-propyl-17?-benzoyloxy-A9-des A-gonene-S
will ‘become obvious from the following detailed descripone, reacting the latter with pyrrolidine to form 5-pyr
r1011,v
The process of the invention comprises reducing a car-
roléiidyl-13,B-n~propy]l-1z?-benzoylgoxying?liiglgdes \Aigfili
na iene, reacting
e atter wit
a
, - '
o u-tene-
o
boxylic acid ester of 13B-alkyl-A4-gonene47,8-ol-3-one
form 3-halo-l3p-n—propyl-l7/3-benzoyloxy-4,5-seco - A2,"
wherein the carboxylic acid is an organic carboxylic acid 35 gonadiene-S-one, hydrolyzing the latter to form 13,8-n
having 1 to 18 carbon atoms and the alkyl group has 1 to
propyl-l7B-benzoyloxy-4,5-seco-A9-gonene~3,S-dione, re
18 carbon atoms with an alkali metal borohydride to form
a carboxylic acid ester of 13?-alkyl-A4-gonene-3,175-diol,
ducing the latte; t5) form 13fl-n-propg?-lZ?-benzogloxyf,5
seco-gonane—3, - ione, con ensing
e atter to orm 3,8
reacting the latter under alkaline conditions to form 13(3n-propyl-l7(3-bcnzoyloxy-M-gonene-3-one and recovering
alkyl-A4-gonene-3,17?-diol, selectively oxidizing the allylic 40 the latter.
hydroxy group of the latter to form 13B-alkyl’A4-gonene17 -01-3-0ne and recovering the latter,
I8 ltihe following11 example hthere ‘are described several
em 0 iment‘s IO ' ustrate t 6 invention.
However, it
[2 preferred mode of the process of the invention comwould be understood that the invention is not intended to
prises reacting the carboxylic acid ester of the 13 ?-alkylbe limited to the Speci?c embodiments.
A4-gonene-l7?-ol-3-one with sodium borohydride to form ‘3:5
EXAMPLE
the carboxylic acid ester of l3f3-alkyl-A4-gonene-3,175-
diol, reacting the latter with an alkaline base such as an
alkali metal hydroxide in a lower alkanol such as meth-
_
5311707117661"?0”v 0f the BenZOate 0f l3?'n-propyl-A4-gonene
17.3'0l-3'0’le (0" 1 8:1 9411.410?'1 35-71-17?‘opyl'testosterone)
anol or ethanol to form 13,8-alkl-A4-gonene-3,17B-diol, _
Step A: 0.5 gm. of the benzoate of l35-n-propyl-A4
oxidizing the latter with manganese dioxide to form 1313- "0 gonene-17?-ol-3-one, obtained according to the United
alkyl-N-gonene-l7,8-ol-3-one and recovering the latter.
States Patent application Serial No. 96,062, ?led January
The reaction is illustrated in Table I.
19, 1961 was introduced into 10 cc. of methanol. 0.125
TABLE I
R
/\
0A
R
R
c
p
/
/
--—>
O:
OAc
/
-—-->
HO NW
HO ~w
011
3,074,978
d
gm. of sodium borohydride was added while cooling and
the reaction mixture was agitated overnight to form a
gonene-l7eol-3-one which comprises reducing a car
boxylic acid ester of 135-n-propyl-A4-goneneal7,8-01-3-one
wherein the carboxylic acid is an organic carboxylic acid
mixture containing the 17?-benzoateof 13?-n-propyl-A4
V gonene-3, 17 ?-diol. .
having 1 to 18 carbon ‘atoms selected from the group con
a Step B: To the mixture 2.5 cc. of a 10% solution of
sisting of alkanoic acids, alkenoic acids, cycloalkyl al
potassium hydroxide in methanol were ‘added and the mix
kanoic acids, phenyl carboxylic acids and phenyl alkanoic
ture was heated to re?ux for a period of four hours. ~ The
acids with an alkali metal borohydride ‘to form the corre
mixture was concentrated to a small volume and poured
sponding 17-carboxylic acid ester of l'a'?-n-propyhM
into {iced water. The precipitated product was vacuum
gonene-3,17B-diol, reacting the latter under alkaline con
?ltered, washed with water, dried and 393 mg. of raw 135 10 ditions to form 13?-n-propyl-M-gonene6,lT?-diol, oxidiz
n-propyl-A4-gonene-3,17?-diol were obtained.
ing the latter with manganese dioxide to form 1313m
‘This product is not described in theliterature.
propyl-A‘i-gonene-l7,8-01-3-one and recovering the latter.
Step ,C: This last compound was dissolved in 80 cc. of
dichlorethane. 2 gm. of-manganese dioxide were added
2. The process of claim 1 wherein the ‘alkali metal boro
hydride is sodium borohydride.
andthe mixture was agitated at room temperature for a 15
‘period of two hours. Theexcess manganese dioxide was
?ltered, the ?ltrate was evaporated to dryness under vac
uum, and 0.400 gm. of product was obtained which was
3. A process for the preparation of 1‘3=;3-n—propy1—A4
gonene-l7/3-ol-3-one which comprises reducing the hen
zoic acid ester of 1El?-n-propyl-M-gonene-l7f3-ol-3-one
, with sodium borohydride to form the benzoic acid ester
puri?ed by chromatography over silica gel. dilution with
of l3B~n-propyl-A4-gonene-3,175-diol, reacting the latter
methylene chloride containing 0.1% of methanol and 20 in ya lower alkanol under alkaline conditions to form 13/]
0.5% of acetone supplied 250'v mg. of lB?-n-propyl-M
n~propyl-A4-gonene-3;17,8-diol, oxidizing the latter with
‘gonene-17/8-ol-3-one having a melting point of 163° ‘C.
manganese dioxide to form 13?-n-propyl-A4-gonene-17B
and a speci?c rotation [a]D20=+64° (c.=Oi.5% in
methanol).
'
Ultraviolet ‘spectra (ethanol) t'ymax_ at 240-241 mp; 25.
6:16,“)0.
Various modi?cations of the process may be made with
v out departing from the spirit or scope ,of the invention
and it is to be understood that the invention is to be
limited only as de?ned in the appended claims. '
30
'
ol-3 -one and recovering the latter.
We claim:
1.,A process for the preparation of 13?-n~propyl-A4
5. 13/3-n-propyl-17e-benzoyloxy-A4-gonene-3-01.
References Qited in the ?le of this patent
UNITED STATES PATENTS
3,012,941
'7 3,014,985
Wettstein et al _________ __ Dec. 12, 1961
Counsell _________ _.|____ Dec. 26, 1961
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