JPH01290680A - Separation of cis type quinuclidine derivative - Google Patents
Separation of cis type quinuclidine derivativeInfo
- Publication number
- JPH01290680A JPH01290680A JP12126888A JP12126888A JPH01290680A JP H01290680 A JPH01290680 A JP H01290680A JP 12126888 A JP12126888 A JP 12126888A JP 12126888 A JP12126888 A JP 12126888A JP H01290680 A JPH01290680 A JP H01290680A
- Authority
- JP
- Japan
- Prior art keywords
- msoq
- perchlorate
- acid
- quinuclidine
- solvent
- 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
- 238000000926 separation method Methods 0.000 title description 11
- UANSQQFYKHHDJM-KRWDZBQOSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]naphthalene-1-carboxamide Chemical compound C1=CC=C2C(C(N[C@@H]3C4CCN(CC4)C3)=O)=CC=CC2=C1 UANSQQFYKHHDJM-KRWDZBQOSA-N 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 26
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims abstract description 23
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000002253 acid Substances 0.000 claims abstract description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000002904 solvent Substances 0.000 claims abstract description 14
- 238000001640 fractional crystallisation Methods 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 150000001298 alcohols Chemical class 0.000 claims description 3
- 150000002576 ketones Chemical class 0.000 claims description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 2
- 235000019253 formic acid Nutrition 0.000 claims description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 abstract description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract description 12
- 201000010099 disease Diseases 0.000 abstract description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
- 238000001816 cooling Methods 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 abstract 2
- 229940057952 methanol Drugs 0.000 abstract 1
- 210000005036 nerve Anatomy 0.000 abstract 1
- 239000002994 raw material Substances 0.000 abstract 1
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 230000001713 cholinergic effect Effects 0.000 description 3
- 208000013403 hyperactivity Diseases 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- WJJSZTJGFCFNKI-UHFFFAOYSA-N 1,3-oxathiolane Chemical group C1CSCO1 WJJSZTJGFCFNKI-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- MQAWJBXBNHAYLJ-UHFFFAOYSA-N 1,3-benzodithiol-3-ium;perchloric acid Chemical compound OCl(=O)(=O)=O.C1=CC=C2[S+]=CSC2=C1 MQAWJBXBNHAYLJ-UHFFFAOYSA-N 0.000 description 1
- OBEOJOQKVZXCRH-UHFFFAOYSA-N 3-(sulfanylmethyl)-1-azabicyclo[2.2.2]octan-3-ol Chemical compound C1CC2C(O)(CS)CN1CC2 OBEOJOQKVZXCRH-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- XTEGARKTQYYJKE-UHFFFAOYSA-N chloric acid Chemical class OCl(=O)=O XTEGARKTQYYJKE-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は、２−メチルスピロ（１，３−オキサチオラン
−５，３０）キヌクリジン（以下ＭＳＯＱと略す）から
、分別結晶法により、高純度のシス型異性体を工業的に
得ることができる分離方法である。この方法によって得
られるシス型異性体は、哺乳類の中枢神経の病気、特に
コリン作用性機能亢進による病気の治療に存効である。DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention is directed to the production of high-purity sys- This is a separation method that allows type isomers to be obtained industrially. The cis isomer obtained by this method is effective in treating diseases of the central nervous system in mammals, especially diseases caused by cholinergic hyperactivity.
（従来の技術）
本発明でいうＭＳＯＱは特開昭６１−２８０４９７号公
輻に記載されている。またこの公報には３−ヒドロキシ
−３−メルカプトメチルキヌクリジンとアセトアルデヒ
ドとを三弗化ホウ素エーテル；１）化合物の存在下で環
化反応をさせてＭＳＯＱを得、次いで分別結晶法並びに
アルミナカラムクロマトグラフィーを併用してＭＳＯＱ
のシス型異性体を得る方法についても記載されているが
、この分別結晶法はＭＳＯＱのトランス型異性体を結晶
化させているため目的とするシス型異性体の純度はせい
ぜい９０％前後であり、さらに高純度とするのは困難を
極める。(Prior Art) The MSOQ referred to in the present invention is described in Japanese Patent Application Laid-Open No. 61-280497. This publication also describes that 3-hydroxy-3-mercaptomethylquinuclidine and acetaldehyde are subjected to a cyclization reaction in the presence of boron trifluoride ether; MSOQ using chromatography
A method for obtaining the cis isomer of MSOQ is also described, but since this fractional crystallization method crystallizes the trans isomer of MSOQ, the purity of the desired cis isomer is around 90% at most. , it is extremely difficult to achieve even higher purity.
（発明が解決しようとする課題）
ＭＳＯＱを製造する際には幾何異性体であるシス型２−
メチルスピロ（１，３−オキサチオラン−５，３’）キ
ヌクリジン（以下Ｃ−ＭＳＯＱと略す）及びトランス型
２−メチルスピロ（１，３−オキサチオラン−５，３０
）キヌクリジン（以下Ｔ−ＭＳＯＱと略す）が生成し、
これらのうちＣ−ＭＳＯＱが補乳頚の中枢神経の病気、
特にコリン作用性機能亢進による病気の治療により有効
であることから、高純度のＣ−ＭＳＯＱを工業的有利に
分離する方法が求められている。(Problem to be solved by the invention) When producing MSOQ, the cis-type 2-
Methylspiro(1,3-oxathiolane-5,3')quinuclidine (hereinafter abbreviated as C-MSOQ) and trans-2-methylspiro(1,3-oxathiolane-5,30)
) Quinuclidine (hereinafter abbreviated as T-MSOQ) is produced,
Among these, C-MSOQ is a disease of the central nervous system of the milk supplemented neck,
Since it is particularly effective in treating diseases caused by cholinergic hyperactivity, there is a need for an industrially advantageous method for separating highly purified C-MSOQ.
（課題を解決するための手段）
本発明者等は、Ｃ−ＭＳＯＱの分離について分別結晶法
に注目し、特開昭６１−２８０４９７号公＋＋＋に記載
の分別結晶法とは逆のＣ−ＭＳＯＱを結晶化させること
によりＴ−ＭＳＯＱと不純物を同時に除くことについて
検討したところ、ＭＳＯＱを予め過塩素酸塩とし、この
塩に溶媒並びに特定の酸を加えた後、冷却すれば、Ｃ−
ＭＳＯＱを結晶化できるとの知見を得た。この知見によ
り、高純度のＣ−ＭＳＯＱの工業的有利な分離方法であ
る本発明を完成するに至った。(Means for Solving the Problems) The present inventors focused on a fractional crystallization method for the separation of C-MSOQ, which is opposite to the fractional crystallization method described in JP-A-61-280497+++. We investigated the possibility of simultaneously removing T-MSOQ and impurities by crystallizing T-MSOQ, and found that if MSOQ is made into a perchlorate salt in advance, a solvent and a specific acid are added to this salt, and then cooled, C-MSOQ can be removed simultaneously.
We have found that MSOQ can be crystallized. This knowledge led to the completion of the present invention, which is an industrially advantageous separation method for highly pure C-MSOQ.
すなわち、本発明は、２−メチルスピロ（１゜３−オキ
サチオラン−５，３０）キヌクリジンからシス型の該キ
ヌクリジンを分別結晶法により分離する方法において、
該キヌクリジンを予めｉ！塩素酸塩とし、この塩に溶媒
並びに酸を加えた後、冷却してシス型の該キヌクリジン
を結晶化させることを特徴とする、シス型の該キヌクリ
ジンの分離方法である。That is, the present invention provides a method for separating cis-type quinuclidine from 2-methylspiro(1°3-oxathiolane-5,30)quinuclidine by a fractional crystallization method,
The quinuclidine in advance! This is a method for separating cis-type quinuclidine, which is characterized in that it is converted into a chlorate salt, a solvent and an acid are added to this salt, and then cooled to crystallize the cis-type quinuclidine.
で表されるが、これは
幾何異性体であるＴ−ＭＳＯＱとＣ−ＭＳＯＱを含む、
Ｔ−ＭＳＯＱは１．３−オキサチオラン環上の２−位の
メチル基とキヌクリジン環の１’−位の窒素原子とが、
１．３−オキサチオラン環の面に対して反対の側に位置
するものであり、一方Ｃ−ＭＳＯＱは２−位のメチル基
と１° −位の窒素原子とが、１，３−オキサチオラン
環の面に対して同じ側に位置するものである。This is represented by the geometric isomers T-MSOQ and C-MSOQ,
T-MSOQ has a methyl group at the 2-position on the 1,3-oxathiolane ring and a nitrogen atom at the 1'-position of the quinuclidine ring,
The methyl group at the 2-position and the nitrogen atom at the 1°-position of C-MSOQ are located on the opposite side of the 1,3-oxathiolane ring. They are located on the same side of the plane.
またＴ−ＭＳＯＱ及びＣ−ＭＳＯＱは各々鏡像異性体を
有する。Moreover, T-MSOQ and C-MSOQ each have enantiomers.
（発明の開示） 本発明の分離方法について説明する。(Disclosure of invention) The separation method of the present invention will be explained.
本発明の分離方法で用いられるＭＳＯＱの純度は、いか
なるものでもよいが、公知の分別結晶法により予めＣ−
ＭＳＯＱの純度を９０％程度にしたものを用いるとより
望ましい。The purity of MSOQ used in the separation method of the present invention may be of any purity, but it must be pre-treated with C-
It is more desirable to use MSOQ with a purity of about 90%.
本発明の分離方法の実施に際して、まずＭＳＯＱを予め
過塩素酸塩とする。この方法としては例えば、ＭＳＯＱ
を）８媒に？８解し、そこへ過塩′Ａ酸を加え、生成し
たＭＳＯＱの過塩素酸塩を通常の方法により濾別・乾燥
する方法が挙げられる。ここで用いる溶媒としてはＭ
Ｓ ＯＱを溶解し、かつ生成したＭＳＯＱの過塩素酸塩
を溶解しないものであればいずれものでもよい０次に前
段で得られたＭＳＯＱの過塩素酸塩に溶媒並びに酸を加
え溶解した後、冷却してＣ−ＭＳＯＱを結晶化させ、そ
の後通常の方法により濾別・乾燥して、目的のＣ−ＭＳ
ＯＱを得る。ここで用いる溶媒としては、メタノール、
エタノールなどのアルコール類、アセトン、メチルエチ
ルケトンなどのケトン１ｎオよび水が挙げられ、これら
溶媒のなかではメタノールが望ましく、これら溶媒の使
用１はＭＳＯＱの過塩素酸塩１重量部に対して１〜１５
重■部、望ましくは水の場合５〜ｌＯ重工部、アルコー
ル類及びケトン類の場合１〜６重ゴ部である。酸として
は塩酸、蟻酸及び酢酸が２１！げられ、これらの酸の中
では酢酸が望ましく、これら酸の使用量はＭＳＯＱの過
塩素酸塩１モルに対して０．２〜１モル、望ましくは０
．２〜０．７モルである。この溶媒及び酸を加える温度
はＭＳＯＱの過塩素酸塩が）宿弊する温度であればいず
れでもよいが、普通４０℃〜溶媒の沸点が望ましい、冷
却はＣ−ＭＳＯＱが結晶化する温度であればいずれでも
よいが、普通１０℃以下が望ましい。When carrying out the separation method of the present invention, MSOQ is first converted into a perchlorate salt. This method includes, for example, MSOQ
) to 8th medium? 8, add persalt A acid thereto, and filter and dry the MSOQ perchlorate produced by a conventional method. The solvent used here is M
Any solution may be used as long as it dissolves SOQ and does not dissolve the generated MSOQ perchlorate. Next, add a solvent and acid to the MSOQ perchlorate obtained in the previous step and dissolve it. The C-MSOQ is crystallized by cooling, and then filtered and dried in a conventional manner to obtain the desired C-MS.
Obtain OQ. The solvent used here is methanol,
Examples include alcohols such as ethanol, ketones such as acetone and methyl ethyl ketone, and water. Among these solvents, methanol is preferable.
It is preferably 5 to 1 O parts in the case of water, and 1 to 6 parts in the case of alcohols and ketones. As acids, hydrochloric acid, formic acid and acetic acid are 21! Among these acids, acetic acid is preferable, and the amount of these acids used is 0.2 to 1 mol, preferably 0.
．． It is 2 to 0.7 mol. The temperature at which this solvent and acid are added may be any temperature as long as the perchlorate of MSOQ is present, but it is generally desirable to use a temperature between 40°C and the boiling point of the solvent. Although any temperature may be used, a temperature of 10°C or less is generally desirable.
本発明の分離方法は、下記の利点を有することから工業
的有利な方法である。The separation method of the present invention is an industrially advantageous method because it has the following advantages.
＋１１ 目的物を９５％以上の高純度で得ることがで
きる。+11 The target product can be obtained with a high purity of 95% or more.
（２）本性は、公知の分別結晶法の改良法であることか
ら、分離操作が前便である。(2) Since this is an improved method of the known fractional crystallization method, the separation operation is a preliminary step.
（実施例）
本発明方法をより詳しく説明するため以下の実施例を記
載するが、本発明方法はこの実施例のみに限定されるも
のではない。(Examples) The following examples will be described to explain the method of the present invention in more detail, but the method of the present invention is not limited to these examples.
実施例１
＋１） Ｍ Ｓ ＯＱの過塩素酸塩の調装ＭＳＯＱ
（Ｃ−ＭＳＯＱの純度９２．３％）８．４ｇをノルマル
ヘキサン５０−に加え撹拌しながら、そこへ過塩素酸２
．１２ ｇを水に熔解した？８液３．５４ｇを５分間に
亘って滴下し、続いて１時間撹拌した。Example 1 +1) Preparation of Perchlorate of MSOQ MSOQ
(Purity of C-MSOQ 92.3%) 8.4g was added to 50% of normal hexane and while stirring, perchloric acid 2.
．． Did you dissolve 12 g in water? 3.54 g of liquid 8 was added dropwise over 5 minutes, followed by stirring for 1 hour.
生成した結晶を減圧濾別し、この結晶をノルマルヘキサ
ンで洗浄後、室温で乾燥し、９．７８のＭＳＯＱの過塩
素酸塩を得た（このＣ−ＭＳＯＱの純度は９２．３％で
あった）。The generated crystals were filtered under reduced pressure, washed with n-hexane, and dried at room temperature to obtain a perchlorate with an MSOQ of 9.78 (the purity of this C-MSOQ was 92.3%). Ta).
＋２１ Ｃ−Ｍ Ｓ ＯＱの分離
前記工程（１１で得られたＭＳＯＱの過塩素酸塩０．５
ｇを２０−の試験管に採り、メタノール０．９５Ｍ！及
び酢酸０．０５Ｍｆｆ１の混合液に加え、６０〜６５℃
で前記の塩を溶解した後、３〜５℃に冷却してそのまま
２日間静置し、成長した結晶を濾別・乾燥してＣ−ＭＳ
ＯＱの過塩Ｔ：酸塩０．２７ｇを得た（このＣ−ＭＳＯ
Ｑの純度は９８．５％であった）。+21 Separation of C-M S OQ perchlorate of MSOQ obtained in step 11 (0.5
g in a 20-liter test tube and add methanol 0.95M! and 0.05Mff1 of acetic acid, and heated to 60-65°C.
After dissolving the above salt, it was cooled to 3 to 5°C and left as it was for 2 days, and the grown crystals were filtered and dried and analyzed by C-MS.
Obtained 0.27 g of OQ persalt T:acid acid (this C-MSO
The purity of Q was 98.5%).
実施例２及び３
前記実施例１の工程＋１１において、過塩素酸塩２．１
２ｇを水に溶解した溶液３．５４ｇに代えて過塩素酸塩
１．２”１ｇを水に溶解した溶液２．１２ ｇ或いは過
塩素酸塩２．９６ｇを水に溶解した溶液４．９６ｇを用
いる以外は同様にしてＭＳＯＱの過塩素酸塩を得た。Examples 2 and 3 In step +11 of Example 1, perchlorate 2.1
Instead of 3.54 g of a solution of 2 g of perchlorate dissolved in water, use 2.12 g of a solution of 1 g of perchlorate dissolved in water or 4.96 g of a solution of 2.96 g of perchlorate dissolved in water. A perchlorate of MSOQ was obtained in the same manner except that the following procedure was used.
実施例４及び５
前記実施例１の工程（１）で得られたＭＳＯＱの過塩素
酸塩を用いて、前記実施例１の工程（２）に串じてＣ−
ＭＳＯＱの分離を行った例を第１表に示す。Examples 4 and 5 Using the perchlorate of MSOQ obtained in step (1) of Example 1, C-
Table 1 shows examples of MSOQ separation.
第１表
（発明の効果）
本発明は、幾何異性体を含有する２−メチルスピロ（１
，３−オキサチオラン−５，３’）キヌクリジンを改良
された分別結晶法により分離して９５％以上の高純度の
シス型２−メチルスピロ（１，３−オキサチオラン−５
，３’）キヌクリジンを得ることができる工業的有利な
分な方法である。この方法によって得られるシス型異性
体は哺乳類の中枢神経系の病気、特にコリン作用性機能
亢進による病気の治療に有効である。Table 1 (Effects of the Invention) The present invention provides 2-methylspiro (1
, 3-oxathiolane-5,3') quinuclidine was separated by an improved fractional crystallization method to obtain cis-type 2-methylspiro(1,3-oxathiolane-5) with a purity of over 95%.
, 3') is an industrially advantageous method for obtaining quinuclidine. The cis isomer obtained by this method is effective in treating diseases of the mammalian central nervous system, especially diseases caused by cholinergic hyperactivity.
Claims (1)
３０）キヌクリジンからシス型の該キヌクリジンを分別
結晶法により分離する方法において、該キヌクリジンを
予め過塩素酸塩とし、この塩に溶媒並びに酸を加え溶解
した後、冷却してシス型の該キヌクリジンを結晶化させ
ることを特徴とする、シス型の該キヌクリジンの分離方
法。 ２、前記溶媒が水、アルコール類及びケトン類から選ば
れた少なくとも１種である、特許請求の範囲第１項に記
載の方法。 ３、前記酸が塩酸、蟻酸及び酢酸から選ばれた１種であ
る、特許請求の範囲第１項に記載の方法。[Claims] 1,2-methylspiro(1,3-oxathiolane-5,
30) In a method of separating the cis-type quinuclidine from quinuclidine by a fractional crystallization method, the quinuclidine is made into a perchlorate salt in advance, and a solvent and an acid are added to this salt to dissolve it, and then cooled to separate the cis-type quinuclidine. A method for separating the cis-type quinuclidine, the method comprising crystallizing the quinuclidine. 2. The method according to claim 1, wherein the solvent is at least one selected from water, alcohols, and ketones. 3. The method according to claim 1, wherein the acid is one selected from hydrochloric acid, formic acid, and acetic acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12126888A JPH01290680A (en) | 1988-05-18 | 1988-05-18 | Separation of cis type quinuclidine derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12126888A JPH01290680A (en) | 1988-05-18 | 1988-05-18 | Separation of cis type quinuclidine derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH01290680A true JPH01290680A (en) | 1989-11-22 |
Family
ID=14807046
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP12126888A Pending JPH01290680A (en) | 1988-05-18 | 1988-05-18 | Separation of cis type quinuclidine derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01290680A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0683168A1 (en) * | 1994-05-19 | 1995-11-22 | Ishihara Sangyo Kaisha, Ltd. | Method for producing 2-methylspiro(1,3-oxathiolane-5,3')quinuclidine |
| WO2000041691A1 (en) * | 1999-01-14 | 2000-07-20 | Snow Brand Milk Products Co., Ltd. | Dry skin remedies |
-
1988
- 1988-05-18 JP JP12126888A patent/JPH01290680A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0683168A1 (en) * | 1994-05-19 | 1995-11-22 | Ishihara Sangyo Kaisha, Ltd. | Method for producing 2-methylspiro(1,3-oxathiolane-5,3')quinuclidine |
| EP1004586A2 (en) * | 1994-05-19 | 2000-05-31 | Ishihara Sangyo Kaisha, Ltd. | Method for producing 2-methylspiro(1,3-Oxathiolane-5,3')quinuclidine |
| EP1004586A3 (en) * | 1994-05-19 | 2001-09-12 | Ishihara Sangyo Kaisha, Ltd. | Method for producing 2-methylspiro(1,3-oxathiolane-5,3')quinuclidine |
| WO2000041691A1 (en) * | 1999-01-14 | 2000-07-20 | Snow Brand Milk Products Co., Ltd. | Dry skin remedies |
| US6410557B2 (en) | 1999-01-14 | 2002-06-25 | Daiichi Pharmaceutical Col, Ltd. | Dry skin remedies |
| AU760180B2 (en) * | 1999-01-14 | 2003-05-08 | Daiichi Pharmaceutical Co., Ltd. | Dry skin remedies |
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