JPS62277396A - Production of high-purity estradiol-3-benzoate - Google Patents
Production of high-purity estradiol-3-benzoateInfo
- Publication number
- JPS62277396A JPS62277396A JP12085686A JP12085686A JPS62277396A JP S62277396 A JPS62277396 A JP S62277396A JP 12085686 A JP12085686 A JP 12085686A JP 12085686 A JP12085686 A JP 12085686A JP S62277396 A JPS62277396 A JP S62277396A
- Authority
- JP
- Japan
- Prior art keywords
- benzoate
- estradiol
- added
- purity
- double bond
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- UYIFTLBWAOGQBI-BZDYCCQFSA-N Benzhormovarine Chemical compound C([C@@H]1[C@@H](C2=CC=3)CC[C@]4([C@H]1CC[C@@H]4O)C)CC2=CC=3OC(=O)C1=CC=CC=C1 UYIFTLBWAOGQBI-BZDYCCQFSA-N 0.000 title claims abstract description 16
- 229960001359 estradiol 3-benzoate Drugs 0.000 title claims abstract description 14
- 238000004519 manufacturing process Methods 0.000 title claims description 3
- 239000012535 impurity Substances 0.000 claims abstract description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 abstract description 21
- 239000003054 catalyst Substances 0.000 abstract description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 abstract description 8
- 238000002425 crystallisation Methods 0.000 abstract description 8
- 230000008025 crystallization Effects 0.000 abstract description 8
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 7
- 239000001257 hydrogen Substances 0.000 abstract description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 5
- 239000002904 solvent Substances 0.000 abstract description 5
- 238000010438 heat treatment Methods 0.000 abstract description 4
- 229910052763 palladium Inorganic materials 0.000 abstract description 4
- 239000003960 organic solvent Substances 0.000 abstract description 3
- 206010002659 Anovulatory cycle Diseases 0.000 abstract description 2
- 239000003795 chemical substances by application Substances 0.000 abstract description 2
- 229940088597 hormone Drugs 0.000 abstract description 2
- 239000005556 hormone Substances 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract 2
- 229950002007 estradiol benzoate Drugs 0.000 abstract 2
- 239000007795 chemical reaction product Substances 0.000 abstract 1
- 239000000706 filtrate Substances 0.000 abstract 1
- 238000001914 filtration Methods 0.000 abstract 1
- 239000011541 reaction mixture Substances 0.000 abstract 1
- 239000013078 crystal Substances 0.000 description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 238000005984 hydrogenation reaction Methods 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 239000000203 mixture Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- -1 methanol and ethanol Chemical compound 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- 201000000736 Amenorrhea Diseases 0.000 description 1
- 206010001928 Amenorrhoea Diseases 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical group [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- 241000283986 Lepus Species 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 231100000540 amenorrhea Toxicity 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- POZRVZJJTULAOH-LHZXLZLDSA-N danazol Chemical compound C1[C@]2(C)[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=CC2=C1C=NO2 POZRVZJJTULAOH-LHZXLZLDSA-N 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 230000027758 ovulation cycle Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000010865 sewage Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Landscapes
- Steroid Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
３、発明の詳細な説明
（産業上の利用分野）
本発明は、高純度エストラジオール−３−ベンゾエート
の製造性に関するものである。Detailed Description of the Invention 3. Detailed Description of the Invention (Field of Industrial Application) The present invention relates to the productivity of high purity estradiol-3-benzoate.
エストラジオール−３−ペンゾエートハ、無月経、無排
卵周期症、月経周期異常などの治療に用いられる女性ホ
ルモン剤として有用なものである。Estradiol-3-penzoate is useful as a female hormone agent used in the treatment of amenorrhea, anovulatory cycle disorder, menstrual cycle abnormality, and the like.
（従来の技術と発明が解決しようとする問題点）Ｃ狼に
二重結合を有する不純物を含有フるエストラジオール−
３−ベンゾエートは、薬効や人体に悪影響するものでは
ないが、医薬原体としてはできるだけ純粋な結晶が望ま
しい。(Problems to be solved by the prior art and the invention) Estradiol containing an impurity having a double bond in C-
Although 3-benzoate does not have any adverse effects on medicinal efficacy or the human body, it is desirable that the crystal be as pure as possible as a drug substance.
本発明者等は、上記実情に鑑み、Ｃ環に一部二重結合を
有するエストラジオール−３−ベンゾエートの高純度化
について種々検討した拮果、Ｃ環に二重結合を有するエ
ストラジオール−３−ベンゾエートはカかなか除去する
ことが雅しり、する特定の手段を採用した場合に限υ、
Ｃ環に二重結合を有するエストラジオ−ルー ｊ −ベ
ンゾエートを除去できることを見い出し本発明に弼］達
した。In view of the above circumstances, the present inventors have conducted various studies to improve the purification of estradiol-3-benzoate having a partial double bond in the C ring. It is only possible to remove it elegantly, and only if certain measures are taken to remove it.
The present invention was based on the discovery that estradio-ruj-benzoate having a double bond in the C ring can be removed.
（問題点を解決するための手段）
すなわち未発明の要旨は、不純物としてＣ環に二重結合
を有するエストラジオール−３−ペン／ｘ−トヲ含ｂエ
ストラジオール−３−ベンゾエートを有機溶媒中水素添
加触媒を用いて水添した後、晶析することを特徴とする
高純度エストラジオール−３−ベンゾエートの製造性に
存する。(Means for Solving the Problems) In other words, the gist of the uninvention is that estradiol-3-pene/x-benzoate containing estradiol-3-pene/ The present invention resides in the productivity of high-purity estradiol-3-benzoate, which is characterized by hydrogenation using hydrogen and then crystallization.
以下、本発明の詳細な説明する。The present invention will be explained in detail below.
本発明の製造法では、まずＣ３Ｊに一部二重結合ヲ有す
るエストラジオール−３−ペン・シェードを有機溶媒に
溶解するが、この際の溶媒の使用量は、粗結晶の２〜１
ｏｏｘ量倍であることが好ましい。また溶解温度は一２
０’〜りＯ℃程度が好ましい。有機溶媒の種類としては
、例えば、テトラヒドロフラン、ジオキサンなどのエー
テル類、メタノール、エタノールなどのアルコール類、
ベンゼン、トルエンナトｆ）芳香族１７１゜化水素、酢
酸、酢酸エチル等及びこれらの混合物が挙げられる。In the production method of the present invention, first, estradiol-3-penshade having a partial double bond at C3J is dissolved in an organic solvent.
It is preferable to double the oox amount. Also, the melting temperature is -2
The temperature is preferably about 0' to 0°C. Examples of organic solvents include ethers such as tetrahydrofuran and dioxane, alcohols such as methanol and ethanol,
Examples include benzene, toluene, f) aromatic hydrogen 171, acetic acid, ethyl acetate, and mixtures thereof.
つイテエストラジオールー３−ベンゾエート溶液中に触
媒を添加し、水素雰囲気下、常温・常圧で４〜！時間水
添を行なうが、触媒としては、パラジウム、白金、ニッ
ケル触媒などが挙げられ、なかでもパラジウム触媒が好
ましく、七の使用量は、粗結晶の０，０ ／ 、 ０．
１重量倍であることが好ましい。A catalyst was added to the estradiol-3-benzoate solution, and the mixture was heated under a hydrogen atmosphere at room temperature and pressure for 4~! Hydrogenation is carried out for a period of time, and examples of catalysts include palladium, platinum, and nickel catalysts, with palladium catalysts being preferred among them.
Preferably, it is 1 times the weight.
また、本発明では上述の水添処理に加えて晶析による精
製手段を組み合わせた場合に高品質の結晶を得ることが
できる。Furthermore, in the present invention, high-quality crystals can be obtained when a purification method by crystallization is combined in addition to the above-mentioned hydrogenation treatment.
晶析溶媒として、トルエン、ベンゼン々どの芳香族炭化
水素、メタノール、工ダノールなどのアルコール類、テ
トラヒドロフラン、ジオキサン々どのエーテル類、アセ
トニトリル、ジメチルホルムアミド、ジメチルスルホキ
シド、酢酸、アセトン、メチルエテルケトンなどのケト
ン類、エチレンジクロリド、クロロホルムなどのハロア
ルカン類、酢酸エチル等及びこれらの混合物が挙げられ
、特にトルエンが好ましく用いられる。これらの溶媒の
使用量は２〜７００重量倍である。しかし使用Ｉが多い
と精結晶の回収率が下がるのでλ〜７０重量倍が好まし
い。As a crystallization solvent, aromatic hydrocarbons such as toluene and benzene, alcohols such as methanol and danol, ethers such as tetrahydrofuran and dioxane, and ketones such as acetonitrile, dimethylformamide, dimethyl sulfoxide, acetic acid, acetone, and methyl ether ketone are used. ethylene dichloride, haloalkanes such as chloroform, ethyl acetate, and mixtures thereof, and toluene is particularly preferably used. The amount of these solvents used is 2 to 700 times by weight. However, if too much I is used, the recovery rate of fine crystals decreases, so it is preferable to use λ~70 times by weight.
晶析の操作は通常溶媒の還Ｒ温度で加熱溶解し結晶を完
全溶解し次いでこの混合物をそのままあるいは濃縮操作
俵２Ｑ℃以下の温度に冷却することにより実施される。The crystallization operation is usually carried out by heating and dissolving the crystals at the reflux temperature of the solvent, completely dissolving the crystals, and then cooling the mixture as it is or to a temperature of 2Q° C. or lower in the concentration bale.
この晶析による精製は単独では十分な効果はなく、上述
した水添法とを組み合わせるととｌζより良好な効果が
発揮されるものであり、その組み合わせの順序としては
水添した後、晶析する方法が採用される。This purification by crystallization alone does not have a sufficient effect, but when combined with the hydrogenation method described above, a better effect than lζ is exhibited, and the order of the combination is hydrogenation followed by crystallization. The method will be adopted.
（実施例）
以下本発明を実施例−により詳細に説明するが、本発明
はその要旨を超えない限シ、以下の実施例によシ限定さ
れるものではない。(Examples) The present invention will be explained in detail below using Examples, but the present invention is not limited to the following Examples unless it exceeds the gist thereof.
実施例／
Ｃ環に一部二重結合を含むエストラジオール−３−ベン
ゾエート（純度は下記第１表に示す。）ｊｏｔにテトラ
ヒドロフラン３００ｄ％！チハラジウムー活性炭／、２
ｊ９を加え、水素雰囲気下、常温・常圧で水添を２時間
行なった。ついで容器内を窒素置換したのち、触媒を濾
過し、更にテトラヒドロフラン５Ｑｄで触媒を洗浄した
。このＦ液を減圧乾固したのち、トルエンＪＯＯｔｌを
加え、加熱溶解後、攪拌″７−２θ℃まで冷却した。析
出した結晶を濾過・乾燥し精工ストラジオ−ルー３−ペ
ンゾエートヲｙｒ、ｇｆを得た。この精結晶の純度を第
１表に示す。Example/ Estradiol-3-benzoate containing some double bonds in the C ring (purity is shown in Table 1 below) 300d% of tetrahydrofuran in jot! Thihaladium-activated carbon/2
j9 was added, and hydrogenation was carried out for 2 hours at normal temperature and normal pressure in a hydrogen atmosphere. Next, the inside of the container was purged with nitrogen, and then the catalyst was filtered and further washed with 5Qd of tetrahydrofuran. After drying this F solution under reduced pressure, toluene JOOtl was added, heated to dissolve, stirred and cooled to 7-2θ°C. The precipitated crystals were filtered and dried to obtain Seiko Stradio-3-penzoate, gf. The purity of this fine crystal is shown in Table 1.
実施例λ
ｃ５に一部二重結合を含むエストラジオール−３−ベン
ゾエート！、θｔにテトラヒドロフランｊｌｄ／トルエ
ン２ｓｄ加え、！チパラジウム／活性Ｉｊ！０．２！ｆ
を添加援、水素５！！、囲気下、常温・常圧で水添を３
時間行なった。ついで容器内を蒙素置換したのち触媒を
濾過し、更にテトラヒドロフラン１０ｗｇで触媒を洗浄
した。このＦ液をＮ２気流下、常圧で溶媒４ｔｊ１１１
を留去し、攪拌下２０℃まで冷却した。析出した結晶を
濾過・乾燥し精工ストラジオ−ルー３−ベンゾエートｙ
、２ｒｙを得た。この精結晶の純度を第１表に示す。Example λ Estradiol-3-benzoate containing a partial double bond in c5! , add tetrahydrofuran jld/toluene 2sd to θt,! Chipalladium/Active Ij! 0.2! f
Addition of hydrogen 5! ! , hydrogenation at room temperature and pressure under ambient atmosphere.
I did it for an hour. Next, the inside of the container was replaced with monoxide, the catalyst was filtered, and the catalyst was further washed with 10 wg of tetrahydrofuran. This F solution was added to the solvent 4tj111 under a N2 stream at normal pressure.
was distilled off, and the mixture was cooled to 20° C. with stirring. The precipitated crystals were filtered and dried to obtain Seiko Stradiol-3-benzoate y.
, got 2ry. The purity of this fine crystal is shown in Table 1.
実施例３
Ｃ環に一部二重結合を含むエストラジオール−３−ベン
ゾニー） ｊ、Ｏｆにテトラヒドロフラン２ｊｘｄ、１
％パラジウム−活性炭０．／、２１加え水素雰囲気下、
常温・常圧で水添を２．５時間行なった。ついで容器内
を窒素置換し之のち触媒を一過し、更にテトラヒドロフ
ラン／、Ｊ―で触媒を況浄した。この汚液に水−２４，
Ｊｄを滴下し、２０℃で２時間攪拌した。析出した結晶
を一過・乾燥し精工ストラジオ−ルー３−ベンゾニー）
Ｉｔ、４ｔ’９を得た。この精結晶の純度を第１表に
示す。Example 3 Estradiol-3-benzony partially containing a double bond in the C ring) j, Of tetrahydrofuran 2jxd, 1
% palladium-activated carbon 0. /, 21 plus hydrogen atmosphere,
Hydrogenation was carried out at normal temperature and normal pressure for 2.5 hours. The inside of the container was then purged with nitrogen, and the catalyst was then purged with tetrahydrofuran/J-. Water-24 to this sewage,
Jd was added dropwise, and the mixture was stirred at 20°C for 2 hours. The precipitated crystals were passed through and dried to obtain Seiko Stradio-Rue 3-benzony).
It, 4t'9 was obtained. The purity of this fine crystal is shown in Table 1.
比較例１
ＧＯに一部二重結合を含むエストラジオール−３−ベン
ゾニート！、０ｆにトルエンＪ！ｄ加え、加熱溶解後、
攪拌下２Ｑ℃まで冷却した。Comparative Example 1 Estradiol-3-benzonite containing some double bonds in GO! , Toluene J at 0f! d and after heating and dissolving,
The mixture was cooled to 2Q°C while stirring.
析出した結晶を濾過・乾燥し精工ストラジオ−ルー３−
ベンゾエートｇ、−ｔ ｔ ヲ得た。この精結晶の純度
を第１表に示す。The precipitated crystals are filtered and dried and used as Seiko Stradio Roux 3.
Benzoate g, -t t was obtained. The purity of this fine crystal is shown in Table 1.
比較例２
ｃｉに一部二重結合を含むエストラジオール−ｊ −ヘ
ｙ ７’エートｓ、ｏ ｙにジメチルホルムアミド／！
−加え、３０℃で加熱溶解したのち、内温ｊｒ０へ６０
℃に保ちつつ、メタノール＝！ｄ＠下した。その後、攪
拌下２０′Ｃまで冷却し、析出した結晶を濾過・乾燥し
精工ストラジオ−ルー３−ベンゾエート３．１” ｆ
＠得た。との精結晶の純度を第１表に示す。Comparative Example 2 Estradiol-j-hey 7'ate s containing some double bonds in ci, dimethylformamide/! in o y.
- Add, heat and melt at 30℃, and then reduce the internal temperature to jr0 at 60℃.
methanol while keeping at °C =! d@ lowered. Thereafter, it was cooled to 20'C with stirring, and the precipitated crystals were filtered and dried to obtain Seiko Stradio-Rue 3-benzoate 3.1" f
@Obtained. Table 1 shows the purity of the fine crystals.
比較例３
Ｃ環に一部二重結合を含むエストラジオール−３−ベン
ゾエート５．０１にア七トン１０θｄ加え、加熱溶解後
攪拌下２０℃まで冷却した。Comparative Example 3 To 5.01 ml of estradiol-3-benzoate partially containing a double bond in the C ring, 10 θd of a7ton was added, dissolved by heating, and then cooled to 20° C. with stirring.
析出した結晶を濾過・乾燥し精工ストラジオ−ルー３−
ベンゾエート２．ｄ’ ｆを得た。この精結晶の純度を
第１表に示す。The precipitated crystals are filtered and dried and used as Seiko Stradio Roux 3.
Benzoate 2. d' f was obtained. The purity of this fine crystal is shown in Table 1.
第１表
（純度は液体クロマトグラフィーにより検出）（発明の
効果）
上記第１表に記した結果からも明らかなように、本発明
によればエストラジオール−３−ベンゾエート中に含有
されるＣＷＡに二重結合を有スルエストラジオールー３
−ベンゾニー） ＧＯ効率的に除去することができ、極
めて高品質のエストラジオール−３−ベンゾエートを製
造することができる。Table 1 (Purity detected by liquid chromatography) (Effects of the invention) As is clear from the results shown in Table 1 above, according to the present invention, CWA contained in estradiol-3-benzoate Surestradiol 3 with a heavy bond
-benzony) GO can be efficiently removed and extremely high quality estradiol-3-benzoate can be produced.
出 願 人 三菱化成工業株式会社 代 理 人 弁理士 長谷用 − ほか／名Sender: Mitsubishi Chemical Industries, Ltd. Representative Patent Attorney Hase - Others/names
Claims (1)
オール−３−ベンゾエートを含むエストラジオール−３
−ベンゾエートを水添した後、晶析することを特徴とす
る高純度エストラジオール−３−ベンゾエートの製造方
法(1) Estradiol-3 containing estradiol-3-benzoate having a double bond in the C ring as an impurity
- A method for producing high-purity estradiol-3-benzoate, which comprises hydrogenating benzoate and then crystallizing it.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12085686A JPS62277396A (en) | 1986-05-26 | 1986-05-26 | Production of high-purity estradiol-3-benzoate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12085686A JPS62277396A (en) | 1986-05-26 | 1986-05-26 | Production of high-purity estradiol-3-benzoate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS62277396A true JPS62277396A (en) | 1987-12-02 |
Family
ID=14796640
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP12085686A Pending JPS62277396A (en) | 1986-05-26 | 1986-05-26 | Production of high-purity estradiol-3-benzoate |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS62277396A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995016700A1 (en) * | 1993-12-16 | 1995-06-22 | Yoshikawa Oil & Fat Co., Ltd. | Process for producing high-purity cholesterol |
-
1986
- 1986-05-26 JP JP12085686A patent/JPS62277396A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995016700A1 (en) * | 1993-12-16 | 1995-06-22 | Yoshikawa Oil & Fat Co., Ltd. | Process for producing high-purity cholesterol |
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