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Патент USA US2866809

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2,866,799
I Patented Dec. 30, 1958
v
2
and may have one or several nuclear double bonds. The
2,866,799
number, nature or location ofsuch nuclear substituents
METHQD ‘FOR QQNVERTZNG A 17-20,20-21 BIS
or double bonds does not affect or interfere with the
above process for forming the dihydroxyacetone side
METHYLENEDTGXY OR A 17-20,20-21 BIS-SUB
STITUTED METHYLENEDIOXY STEROID OF
THE PREGNANE SERIES TO A 17a,21-DIHY-.
DROXY-Zll-KETU STEROID OF THE PREGNANE
SERIES
'
chain since the rest'of the molecule does not-participate .
in the reaction. As would be expected, any‘ nuclear
substituents subject to acid hydrolysis will be removed
-
but this is not a fundamental molecular change and in
most cases is incidental to obtainment of a particular
Roger E. Beyier, Westiield, and Lewis H. Sarett, Prince
ton, N. 5., assignors t0 Merck & Co, Inc, Rahway,
type
of
steroid.
.
;
’
'
-
'
-
Serial No. 632,026
As will be‘ seen- from the partial structural formula
above, the starting materials for our process are steroidal
compounds having twohydrogen atoms or one hydrogen
atom and one lower alkyl radical attached’ to each of
12 Claims; (Cl. 260-39145)
two carbon atoms of the bis-dioxy moiety. Such prod-’
. As’ described and claimed in our copending patent ap
aldehyde. Alternatively, a l7-20,20-21 bisethylidenedioxy
(n=l), 17-_20,20-‘2l bispropionaldioxy’ (12:2), 17-20,
N. 5., a corporation’ of New Jersey
_
No Drawing. Application January 2, 1957
nets are made by treating a 17a,21-dihydroxy-20.-keto
steroid ‘of the pregnane series with an aldehyde in the
This invention relates to a process for making steroid
presenceof a strong acid. The nature of these substitu
compounds. More particularly, it relates to a’ process
ents depends, therefore, on the particular aldehyde with
vfor elaborating a dihydroxyacetone side chain attached
to a steroid nucleus. Still more particularly it is con 20 which the ‘1704,21-dihYd1'QXY-20-k6t0 moiety has been in
activated. ‘Thus, we may use, and prefer to use, a
cerned with a method for converting a 17-20,20-21 bis
17-20,20-21 bismethylenedioxy steroid in which the value
methylenedioxy or a 17-20,20-21 bis-substituted methyl
enedioxy steroid of the pregnane series to a 17a,2l
of n in the formula above is O, and which is obtained
by reaction of the 17a,2l-dihydroxy-ZO-ketone with form
dihydroxy~20~keto steroid of the pregnane series.
plications Serial Nos. 632,009 and 632,010, ?led Jan
uary 2, 1957, the dihydroxyacetonemoiety of a steroid
' 20-21 bisbutyraldioxy (1t=3),
17-20,20-21 bisvaleral- '
dioxy (n=4),, ‘or a 17-'20,20-21 biscaproaldioxy (n=5)
compound may be inactivated or “blocked” by treatment
of the .eroid witha suitable aldehyde whereby a 17-20, _
20-21v bismethylenedioxy or 17-20,20-21 bis-substituted
seroid compound of the pregnane series may be obtained
methylenedioxy steroid derivative is formed. Such de
with acetaldehyde, propionaldehyde, butyraldehyde, valet‘?
aldehyde or caproaldehyde, and employed satisfactorily
rivatives are valuable since they permit processes such
as starting material for the'process of this inventionQ.
as a Claisen condensation or a Grignard reaction to be‘
Typical examples of 17-20,2‘0-,21 bismethylenedioxy and
17,20,20-2Ibis-substituted methylenedioxy steroids which
carried out on the steroid nucleus without undesirable
involvement of the dihydroxyacetone side chain. This
side chain is normally at carbon atom 17 of the nucleus
and for this reason the discussion of our invention‘ is
directed to such steroids. It may, of course, be located
” are converted by our process to l7a,21-dihydroxy-20-l<eto
steroids are:
17-20,20-2l-bismethylenedioxy-pregnan-3-o1
17- 4,20-21-bismethylenedioxy-4-pregnen-3-one
at other positions of the nucleus such as at C-16 or
C-17a of a D-homo steroid, and the process of our in
17-20,20_2l-bismethylenedioxy-4épregnene-3,1 ledion'e
17- 20,20 - 21 - bismethylenedioxy'- 1,4 - pregnadiene
vention is equally applicable to such types of steroids.
3,11-dione
It is a purpose of the present invention to provide a
process for reforming the dihydroxyacetone side chain
from the l7-20,20-21 bismethylenedioxy or 17-20,20-21
bis-substituted methylenedioxy steroid. It is a more spe 45
ci?c object to provide a method of treating a 17-20,20-21
_
y
,
17 - 20,20 - 21 - bisethylidenedioxy 3,1l-dione
1,4 - pregnadiene
.
'
t
17 - 20,20 - 21 - bisbutyralidoxy - 9a, - chloro - 4 '- preg
nene-11?-ol-3-one.
20—21 bismethylenedioxy (or bis-substituted methylene
'
'
v
17 -20,20 - 21 - bisvaleraldioxy - 90c - bromo - 4 - preg
dioxy) steroid of the pregnane series with acid, thus
forming a 17ot,21-dihydroxy-20-keto-pregnane. Further
objects will be evident from the discussion of this proc
'
I
l7-20,20-21-bisbutyralidioxy-4-pregnene-3,ll-dione
and a 17ot,21-d1hYd1'OXY-20-k€t0 steroid obtained. A still
more de?nite object is a method of treating a 17-20,
.
‘
l7-20,20-21-bisethylidenedioxy-4-pregnene-1 1,8-ol-3-one .
steroid with acid whereby the bisdioxy group is removed
hereinbelow.
-
17-20-20-21-bisethylidenedioxy-4epregnene-3 ,1 l-dione
bisrnethylelnedioxy (or bis-substituted methylenedioxy)
ess
Y
17 - 20, 20 - 21 - bismethylenedioxy - 1,4 - pregnadiene
1 1/9-ol-3-one
'
nene-11?-ol-3-one
‘
.
~
"
,
.
-
17 - 20,20 - 21 - bismethylenedioxy - 9m - ?uoro - 1,4
.- pregnadiene-ll?-bl-S-one
,
-
-
17 - 20,20 - 21 - bismethylenedioxy - 12oz - ?uoro - 1,4
Our process may be pictured structurally as follows:
pregnadiene-3,1 l-dione
-
,
‘
17,20,20 - 21 - bispropionaldioxy - 4 - pregnene - 6 - ol
3,l1-di0ne
'
'
‘
I 6'01 17 - 20,20 - 21 - bismethylenedioxy - 6 - meth
.pregnadiene-l 1/8-ol-3-one
'
1 - 1,4!
-
17 - 20, 20 - 21 - bismethylenedioxy - 12a - chloro - 4
C-0
pregnene-l l?-ol-B-one
OH
I
~
.
_
17 '- 20,20 - 21 - bismethylenedioxy - 4,6 - pregnadiene
- (StI’)
st
()
65
3,11-dione
\
-
‘
17~ - 20,20- 21 - bismethylenedioxy - 9oz - ?uoro - 4 — preg~
In the above equation n is a whole integer having a value
of O to 5 inclusive. The expression St'is intended to
17 - 20,20 - 21 - bismethylenedioxy - 4 ~ pregnen - 9a,1l?
mean the cyclopentanopolyhydrophenanthrene nucleus
diol-3-one
_ l
with the exception of carbon atom 17 which is separately
17
-20,20-2
1-bismethylenedioxy-alloprcgnane3,
1 l-dione
shown. The steroid condensed ring nucleus may be 70 17 - 20,20 - 21 - bismethylenedioxy - 19 -,nor - 4 - preg—
substituted'at one or several of the nuclear carbon atoms
nene-11?-ol-3-one
,
v
;
.
‘
2,8 66, 799
d
4
.
The 17a,21-dihydroxy-20-keto moiety; either as such
l7-20,20-21-bismethylenedioxy~4-pregnen-6-ol-3-one
' or esteri?ed at positions 17 or 2]., is an integral part of
17 - 20,20 - 21 - bismethylenedioxy - 4,9(11) - pregnadien
3-one
‘
the several steroids which have pronounced cortisone-like
‘
activity.
17 ‘- 20,20 '- 21 - bismethyle‘nedioxyw 9,11 .~ oxide -. 4
preg‘nen-S-one‘“
.
i
17 - 20,20 .-. 211 - bis
3,1l-dione.
‘
‘
has been inactivated or “blocked” as a 17-20,20-21 bis
methylenedioxy -, 1,4‘ .- tpreg'nadiene
.
‘
‘
‘
‘
methylenedioxy-or l7-20,20‘2l bis-substituted methylene
dioxy derivative.
‘
17 - "0,20 . 121 - bism‘ethylenedioxy -1:4 - pregame 5111s- 1
ol-3-one
‘
.
The new process described herein is a ready
method of reforming this part of the molecule after it
“ The following examples are given for purposes of
10 illustration and not by way of limitation:
.
l7,20,20-21¢biscaproaldioxyépregnane-Z‘s,1lldione
, EXAMPLE 1
l7 - 20,20 ‘- 21 ~ bispropionaldioxy- 2 1''‘ methyl - 4 - lpreg
nene-3,ll-dione
.
.
1
.
1.
'
-
17 - 20,20 - 21 - bisethylidenedioxy - 4 - pre'gnen- 9:2,11‘5
diol-3-one
1
‘
1
.
1
.
.
‘In ‘carrying
four‘ process ‘afsfo‘lution ‘or suspension
of the 1712020121 ismet‘hyle‘ri ‘io‘x'yor'17-‘20,20-2l bis
substiu‘ited methylenedioxy steroid of the pregnane series
Cortisone acetate
To 100 mg. of l7-20,20-21-bismethylenedioxy-4-preg
15 nene-3,l1-dione is added 5 ml. of methanol and 5 ml. of
5 N sulfuric acid and the heterogeneous mixture re
?uxed on the steam bath for one hour (homogeneous
after 45 minutes). The methanol is removed in vacuo
is ‘treatednwith ‘acid and preferably with a strong ‘acid.
We ‘prefer ‘to 'use ‘perchloric acid, formic acid, ‘acetic acid
or ‘mineral acids ‘such ‘as hydrochloric, hydrobromic, ‘sul
furic ‘fdrup‘hos'phoric acids, and ‘the like. The reaction
and the resulting aqueous solution ‘thoroughly extracted
20 withethyl acetate.
‘ is preferably brought about in a "one-‘pliase‘solvent system.
When “an ‘organic )acid iscmplo'yed to ‘bring about re
generation or ‘tile dihyd‘r‘oxyacelton‘e side chain, we ?nd
it suitable and convenient ‘to use ‘an excess of ‘the ‘acid
asfthels'olyent‘imedium forj‘the'reaction. For example,
in ‘the, conversion of‘ the‘ ‘17-‘20,20-21 bism‘ethylenedioxy
derivativesof,cortisone and “hydro‘cb'rtisone ‘to the parent
1 ‘ebmpauaas‘ws have‘use'd aceticandformic acids as both 30
The extract is Washed with sodium
bicarbonate, dried and concentrated to give 96 mg. of
residue. This 1is dissolved in 0.3 ml. of pyridine and 0.3
ml. ‘of acetic ‘anhydride. The 'mixture is heated for ten
minutes ‘on the steam bath and poured into water. The
resultant mixture is extracted several times with meth
ylene chloride, the methylene chloride washed with dilute
hydrochloric acid and sodium bicarbonate, dried over
magnesium sulfate and evaporated. The residue is re
crystallized from acetone to .give cortisone acetate.
solvent "and ‘acid. Alternatively, a lower aliphatic 'car
EXAMPLE 2
boiylic, acidfs‘ii'eh "as ‘acetic ‘o'r propionic ‘acid, can serve
as‘ thefisoly‘e ‘ass a ‘stronger acid employedrt‘o bring
about ‘th'e‘r’hydrolysis. Low'er alkanols are ‘another class
Hydrocortisone acetate
To 690 mg. ‘of 17-20,20-21-bismethylenedioxy-lt-preg
ne‘ne-115-ol-3-one is added 50 ml. of 50% acetic acid.
of ‘satisfa‘c‘t‘ory’solvent's‘ for 'the process. “Likewise. a two
This mixture is heated under nitrogen ‘at 100° C. for 61/3
hours. The reaction ‘mixture is then concentrated under
vacuum‘to dryness. The residue is dissolved in 2.0 ml.
p‘hase, tench “system ‘may be ‘utilized, with the steroid
dissolv‘d illa ,iiit‘able water-immiscible organic solvent
such "a; "chloroform, ‘methylene ‘chloride, benzene 'and the
like‘. The”oi‘ga‘riic phase and ‘aqueous acidic ‘I‘pha'se‘ are
mixed by agitation to effect the reaction.
‘ ‘
p
The reaction ‘times‘and temperatures ‘are not critical,
410
and optimum ‘conditions‘will ‘vary with ‘the particular
steroidYs‘ta‘rt‘in'g‘.‘material and ‘acidic reagent employed.
Generally, we obtain optimum ‘results at ‘temperatures
aqueous sodium bicarbonate. Drying and evaporation
of methylene chloride gives'742 mg. ‘of crude hydro
cortisonej acetate. Chromatography on alumina yields
substantially ‘pure hydrocortisone acetate in the ether
chloroforin (3 to 7, 2 to 8, and 1 to 9) e?luents.
rangingfrom about 15f’ C. up to about 100"’ C.,‘ and
at*‘reacti‘o‘n‘1times1 ‘of about 30 minutes to about ‘50 hours.
We prefer to carry out our process at about 25-75“ C.
for about three totenhou‘rs.
‘
.
of pyridine and 1.8 ml. of acetic anhydride and kept at
room‘t'emperature for 18‘ hours. After pouring into water
the mixture is extracted several times with methylene
chloride. The combined methylene chloride extracts
are 'w'asherl‘with 2.5 N hydrochloric acid and saturated
‘
In the same manner, and using 540 mg. of 17-20,.20
With any particular 17720,20-2l bismethylenedioxy (or
bis-substituted methylenedioxy st‘e'roid)‘or ‘acidic reagent
Zl-bismethylenedioxy-l,4-pregnadiene - 3,11 - dione as
starting material, prednisone acetate is obtained.
the cou‘rse'of the reaction and ‘the ‘best operating condi
tions can be ‘easilyand ‘readilylde'te'i-‘mined by an assay
EXAMPLE 3
with jdianisole ‘ bisdiphenylt'etrazolium"chloride, otherwise
Cortisone acetate
known as the RT. reagent. With this assay,‘ a 1711,21
dihydroxyHZO-ke'to ‘steroid"will1'give with ‘the B. T. re
agent and under the conditions describéd‘tby‘Mader ‘et al.,
Anal. Chem, 24, 666 ‘(19521) "a
'color. The
intensity of the color, which is easily ‘measurable quahtita~ ‘
tively against a standard “solution, 'is a measure ‘of the
amount of 1711,21-dihydroxy120-ltetolsteroid‘ present 1 since
the -l7-20,'20-2¢11bisdioxy ‘s't'artingl‘r‘n'aterials of ‘our process
do not give a positive test in ‘the B. T, assay. “
‘
At “the‘ completion 'ef1our-1prec'eg's, ‘the formed‘?all
60
200mg. of 17-20,20-21-bismethylenedioxy-4-pregnene~
3,1‘l-dione in 2.0 ml. of 198-100% formic acid is heated
at 80° ‘C. for 20’ minutes. After cooling it is poured into
about 10 ml. of water and extracted several times with
methylene chloride. The combined solvent extracts are
washed with saturated sodium bicarbonate solution, dried
and concentrated to yield 203 mg. of semicrystalline prod
uct. Hydrolysis of this product with sodium methoxide
dihydroxy-ZO-keto steroid is isolated ‘ibylany or thef‘méth
in methanol, followed by acetylation of the hydrolysis
product with acetic anhydride-pyridine yields cortisone
ods known to. those skilled‘ in the "steroid ‘art. - For‘ex
acetate.
ample, the reaction solvent may‘ belremovedby‘ concen
tration and the steroid'ektrhote'd Pinto‘ a water-immiscible
organic solvent. The solvent is then removed 1and the
desired ‘compound obtained lineuhs't'antially pu‘re‘for'm
from the residue by chromatography on alumina‘n- ‘We
prefer to form a C-21 ester of ‘the 'steroid‘with a lower
aliphatic carboxylic acid after removal of the‘reaction
solvent but ‘prior to any puri?cation steps. TThese 21
esters,<and particularly the‘acetates,1’are»‘highly crystalline
compoundsand more readily puri?ed lthan theYfree-zl
alcohols. .
When a mixture of 150 mg. of 17-20,20-21-bismeth
ylenedioxy-1,4-pregnadiene-1l?~ol-3-one is heated at
75° C. for 30 minutes, and the mixture then worked up
as described above, substantially pure prcdnisolone ace
tate is obtained.
EXAMPLE 4
p
l Hydrocortisone
To ‘ 50 ‘mg. "of -1‘7-20,20-21-bismethylenedioxy-4-preg~
nene—ll?-ol-3~one in 2.0 ml. of glacial acetic acid is
2,866,799
added 9.2 mluof 60% perchloric acid. The mixture is‘
kept at room temperature for 11 hours. It is poured
into .water and extracted'sevcralptimes with ethyl acetate.
The combined ethyl acetate extracts are washed,,with
saturated sodium, bicarbonate and concentrated to give
6
form‘solutioniis dried and concentrated to dryness‘ in
vacuo. The residual 4,9(1l)-pregnadien-17a,21-diol-3,20r
diQnejZ‘I-acetate may,’ if desired, be further puri?edby
chromatographing on alumina.
46 mg. of crude hydrocortisone.
EXAMPLE 10
EXAMPLE 5
l 7. .nllegregrtah-ijazz-dialog1,20-rri0ne ZI-acetate
9ay-?uoro-cgrtisone
Following the procedure of Example 9 with 500 vmg.
To 100 mg. of 17-20,20-21-bismethylenedioxy-9a-?u~ 10 of 17-20,20-21-bispropionaldioxy-allopregnane-3,lvl-dione,
oro-4-pregnene-3,11-dione in 2.5 ml. of glacial acetic acid
there is obtained from the chloroform extract allopregnan
is added 0.1 ml. of concentrated hydrochloric acid. After
~ 17a,21-diol-3,11,20-trione 2l-acetate.
42 hours at room temperature the reaction is worked up
In the above examples, the starting materials may be
as described in Example 4 to give 9a-tluorocortisone.
prepared by treating a chloroform solution or suspension
15
of a 17a,21-dihydroxy-20-keto steroid appropriately sub
EXAMPLE 6
stituted or unsaturated in the nucleus with formaldehyde
Cortisone acetate
in the presence of hydrochloric acid to make the 17-20,20
To 100 mg. of 17-20,20-21-bismethylenedioxy-4
21bismethylenedioxy compounds, or with a lower alkyl
pregnene-3,ll-dione in 2.5 ml. glacial acetic acid is added
aldehyde in the presence of hydrochloric acid to make the
0.2 ml. of concentrated sulfuric acid. After 14 hours
17-20,20-21 bis-substituted methylenedioxy compounds.
at room temperature the mixture is treated as in Example
The reaction is conveniently conducted at about 30° C.
4. _A residue is obtained which on further puri?cation ‘ for ?ve hours although for optimum yields the formation
yields substantially pure cortisone.
of bisdioxy compound is followed by means of the B. T.
test referred to above. At the end of the reaction period,
EXAMPLE 7
the two layers are separated, and the aqueous layer ex
6-dehydr0cortisone acetate
tracted with fresh chloroform. The chloroform solutions
are combined, washed with 5% sodium bicarbonate and
A mixture of 200 mg. of 17-20,20-2l-bismethylene
dried. The chloroform is then removed and the residual
dioxy-4-6-pregnadiene-3,1l-dione, 12 ml. of methanol
and 12 ml. of 5 N sulfuric acid is re?uxed for 90 minutes. 30 bisdioxy steroid further puri?ed, if desired, by recrystal- .
lization or chromatographic methods well recognized in
The alcohol is removed by concentration in vacuo, and
the art. ‘
’
the residual solution extrated with three 10 mL-portions
Although
the
above examples are given in order to
of ethyl acetate. The organic extracts are combined,
teach
speci?cally
and to illustrate methods of carrying
washed with dilute sodium bicarbonate and dried over
magnesium sulfate. The solvent is removed in vacuo 35 out our invention, it will be evident that'ordinarily re
actions or transformations are carried out in the nucleus
leaving a residue which is dissolved in a mixture of 1 ml.
of pyridine ‘and 1 ml. of acetic anhydride. After heat
ing on the steam bath for 10 minutes, the mixture is
poured into water, and the aqueous phase extracted with
of the 17-20,20-21 bisdioxy steroid before such compounds
are treated by our process to re-form the dihydroxyacetone
side chain.
What is claimed is:
three '5 ml.-portions of chloroform. The chloroform 40
1. The process which comprises treating a steroid of
solutions are washed with water, acid and base, and dried
the pregnane series having at carbon atoms 17, 20 and 21
over magnesium sulfate. On evaporation of the solvent,
the structure
‘and crystallization of the residue from acetone, 4-6
pregnadien-l7a,2l-diol-3,l1,20-trione 2il-acetate is ob
tained.
'
EXAMPLE 8
6-m‘ethyl prednisone acetate
180 mg. of 17-20,20-21-bismethylenedioxy-6-methy-1,
4-pregnadiene-3,ll-dione in 3 ml. of, glacial acetic acid
is treated with 0.5 ml. of concentrated sulfuric acid, and
the reaction mixture held at 35 ° C. for 10 hours. The
mixture is then poured into water and extracted with
three small portions of methylene chloride. The organic
extracts are combined, washed with dilute sodium bicar
bonate and the solvent removed in vacuo. The residue
is dissolved in pyridine~acetic anhydride as described in
Example 2. The 6-methyl prednisone acetate thus ob
tained is isolated by the procedure set forth in Example 1.
EXAMPLE 9
4,9 (11 ) -pregnadien-1 70:,21 -di0l-3,20-di0ne 21 -acelaz‘e'
55
wherein n is a whole integer having a value of 0 to 5 in
clusive with an acid selected from the class consisting of
perehloric, formic, acetic and mineral acids thereby form
ing a l7a,2l-dihydroxy-ZO-keto steroid of the pregnane
series.
60
2.
3.
4.
5.
The process
The process
The process
The process
'
of claim
of claim
of claim
of claim
1
1
1
1
wherein n is 0.
wherein n is 1.
wherein n is 2.
wherein n is 3.
6. The process which comprises treating a 17-20,20-21
bismethylenedioxy steroid of the pregnane series having
5l0 mg. of 17-2020-21 bisethylidenedioxy-4,9(l l)
at the 3-position a member of the class consisting of keto
pregnadien-3-one is added to 45 ml. of 50% acetic acid
and hydroxy substituents with an acid selected from the
and the resulting mixture heated on the steam bath under
classconsisting of perchloric, formic, acetic and mineral
nitrogen for eight hours. The mixture at the ‘end of
acids thereby forming a l7a,2l-dihydroxy-20-keto steroid
this time is concentrated to dryness in vacuo, and the res
of the pregnane series having at the 3-position a member
idue dissolved in 3.0 ml. of pyridine and 2.0 ml. of acetic
of the class consisting of keto and hydroxy substituents.
anyhydride. This solution is held at 40° C. for 12 hours’ 70
7. The process which comprises treating l7-20,20-21
and then poured into 30 ml. of water.
bismethylenedioxy-4-pregnene-3,1l-dione with sulfuric
The resulting aqueous solution is extracted with three
acid thereby forming 4~pregnene-17a,2l-diol-3,l1,20
20 ml.-portions of chloroform, and the combined solvent
trione.
,
extracts washed successively with 2 N hydrochloric acid,
8. The process which comprises treating 17-20,20-21
5% sodium bicarbonate solution and water. The chloro
bismethylenedioxy-4-pregnene-11,8-ol-3-one with acetic
9,866,799
8
‘~11. The processlwhich comprises treating 17-20,20-21
bismethylenedioxy-1,4-pregn1adiene3,11~dione with formic
acid thereby forming hpredhisone.
10. The process which comprises treating 17-20,20-21
bisrnethylenedioxy-li-pregnene-11B-ol-3-pne with perchlor
ic acid thereby forming ‘4-pregnene-1‘1?,17a;21-tridl-3,20
dione.
‘
t
‘
hydrochloric acid thereby forming 9u~?uorocorti'sone.
“12. Whe ‘process which comprises treating -17-20,20-21
=55 bis‘ethylidenedioxy-4;9( 1 1 ) -pregnadien-3-one with acetic
acid thereby forming 4,9(1'1)'pregnadien-17a,2l-diol
3,20-dione.
No references cited.
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