JPH11180930A - Production of optically active trans-cyclobutanedicarboxylic acids - Google Patents
Production of optically active trans-cyclobutanedicarboxylic acidsInfo
- Publication number
- JPH11180930A JPH11180930A JP35290797A JP35290797A JPH11180930A JP H11180930 A JPH11180930 A JP H11180930A JP 35290797 A JP35290797 A JP 35290797A JP 35290797 A JP35290797 A JP 35290797A JP H11180930 A JPH11180930 A JP H11180930A
- Authority
- JP
- Japan
- Prior art keywords
- optically active
- cyclobutanedicarboxylic
- trans
- formula
- active amine
- Prior art date
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【0001】[0001]
【発明の属する技術分野】本発明は、光学活性trans−
シクロブタンジカルボン酸類の製造方法に関する。[0001] The present invention relates to an optically active trans-
The present invention relates to a method for producing cyclobutanedicarboxylic acids.
【0002】[0002]
【従来の技術】光学活性trans−シクロブタンジカルボ
ン酸類は、抗ウイルス剤等の医薬中間体等として有用な
化合物であるが、従来、ラセミ体を光学分割して製造す
る方法は知られていなかった。従来のラセミ体のtrans
−シクロブタンジカルボン酸類を光学活性化する方法と
しては、特開平5−178857号公報に記載のラセミ
−trans−シクロブタンジカルボン酸類を光学活性2−
フェニルグリシノールと反応させて対応するジアミド化
合物のジアステレオマー混合物を取得し、シリカゲルカ
ラムクロマトグラフィーによる精製後、適当な溶媒中で
一方のジアステレオマーのみを結晶化させる方法が知ら
れている。2. Description of the Related Art Optically active trans-cyclobutanedicarboxylic acids are useful compounds as pharmaceutical intermediates such as antiviral agents, but no method for producing a racemate by optical resolution has been known. Traditional racemic trans
As a method for optically activating cyclobutanedicarboxylic acids, a racemic-trans-cyclobutanedicarboxylic acid described in JP-A-5-178857 can be optically activated.
A method is known in which a diastereomer mixture of a corresponding diamide compound is obtained by reacting with phenylglycinol, purified by silica gel column chromatography, and then only one diastereomer is crystallized in an appropriate solvent.
【0003】[0003]
【発明が解決しようとする課題】上記の方法では、高価
な光学活性2−フェニルグリシノールが必要であるばか
りではなく、2−フェニルグリシノール由来の置換基を
除去するために多段階の工程を必要とする等の問題があ
り、ラセミ−trans−シクロブタンジカルボン酸類を直
接、光学分割する方法の開発が望まれていた。光学活性
なtrans−シクロブタンジカルボン酸類を取得できれ
ば、アルカリ金属水素化物を使用する一般的な還元反応
で、対応する光学活性ジメタノール化合物に、誘導する
ことができる。In the above method, not only expensive optically active 2-phenylglycinol is required, but also a multi-step process for removing a substituent derived from 2-phenylglycinol. There are problems such as necessity, and development of a method for directly optically resolving racemic-trans-cyclobutanedicarboxylic acids has been desired. If an optically active trans-cyclobutanedicarboxylic acid can be obtained, it can be derived to a corresponding optically active dimethanol compound by a general reduction reaction using an alkali metal hydride.
【0004】そこで本発明者らは、ラセミ−trans−シ
クロブタンジカルボン酸類を光学分割する方法を開発す
るべく鋭意検討した結果、本発明の完成に至った。The inventors of the present invention have made intensive studies to develop a method for optically resolving racemic-trans-cyclobutanedicarboxylic acids, and as a result, have completed the present invention.
【0005】[0005]
【課題を解決するための手段】すなわち、本発明は、一
般式(1) (式中、Rは低級アルキル基を示す)で示されるラセミ
−trans−シクロブタンジカルボン酸類に光学活性アミ
ンを作用させていずれか一方のジアステレオマー塩を優
先的に析出させ、得られた塩を酸で分解することによる
一般式(2) (式中、Rは前記と同じである) または一般式(3) (式中、Rは前記と同じである)で示される光学活性tr
ans−シクロブタンジカルボン酸類の製造方法を提供す
るものである。That is, the present invention provides a compound represented by the following general formula (1): (Wherein, R represents a lower alkyl group) by reacting an optically active amine with a racemic-trans-cyclobutanedicarboxylic acid represented by the formula (1) to preferentially precipitate one of the diastereomeric salts. General formula (2) by decomposition with an acid (Wherein R is as defined above) or general formula (3) (Wherein R is as defined above)
An object of the present invention is to provide a method for producing ans-cyclobutanedicarboxylic acids.
【0006】[0006]
【発明の実施の形態】以下、本発明について詳細に説明
する。本発明で原料として使用する上記一般式(1)で
示されるラセミ−trans−シクロブタンジカルボン酸類
において、置換基Rは炭素数1〜6を有する低級アルキ
ル基であって、該アルキル基は直鎖状でも分岐状でもよ
い。かかるラセミ−trans−シクロブタンジカルボン酸
類は、例えば、Tetrahedron Lett., 30, 6453(1989)
に記載の方法に準じてケテン ジアルキルアセタールと
フマル酸ジエチルを原料とする[2+2]反応で対応す
るシクロブタンジカルボン酸ジエチルエステル類を取得
し、これを加水分解することにより容易に製造すること
ができる。BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail. In the racemic-trans-cyclobutanedicarboxylic acids represented by the general formula (1) used as a raw material in the present invention, the substituent R is a lower alkyl group having 1 to 6 carbon atoms, and the alkyl group is a linear alkyl group. However, it may be branched. Such racemic-trans-cyclobutanedicarboxylic acids are described, for example, in Tetrahedron Lett., 30 , 6453 (1989).
The corresponding cyclobutanedicarboxylic acid diethyl esters are obtained by a [2 + 2] reaction using ketene dialkyl acetal and diethyl fumarate as raw materials in accordance with the method described in (1), and can be easily produced by hydrolysis.
【0007】本発明で使用される光学活性アミンは、上
記一般式(1)で示されるラセミ−trans−シクロブタ
ンジカルボン酸類に作用させた際に一方の光学活性tran
s−シクロブタンジカルボン酸と優先的に塩形成するも
のであれば特に制限されないが、特に好ましくは一般式
(4) (式中、*印は不斉炭素原子を示す。R1は水素原子また
は、ベンゼン環上に置換基を有していてもよいベンジル
基を、R2は水素原子またはベンゼン環上に置換基を有し
ていてもよいフェニル基を、R3は水素原子またはメチル
基を示す。)で示される光学活性フェネチルアミン誘導
体が用いられる。The optically active amine used in the present invention is one of the optically active amines when acted on the racemic-trans-cyclobutanedicarboxylic acid represented by the above general formula (1).
The salt is not particularly limited as long as it preferentially forms a salt with s-cyclobutanedicarboxylic acid, but is particularly preferably represented by the general formula (4): (In the formula, * represents an asymmetric carbon atom. R 1 represents a hydrogen atom or a benzyl group which may have a substituent on a benzene ring, and R 2 represents a hydrogen atom or a substituent on a benzene ring. And R 3 represents a hydrogen atom or a methyl group.), Which is an optically active phenethylamine derivative.
【0008】一般式(4)において、R1は水素原子また
は、ベンゼン環上に置換基を有していてもよいベンジル
基を表わし、置換基としては、例えば、上述した低級ア
ルキル基、水酸基、炭素数1〜6の低級アルコキシ基等
が例示できる。ベンゼン環上の置換基は1でも2以上で
もよい。In the general formula (4), R 1 represents a hydrogen atom or a benzyl group which may have a substituent on the benzene ring, and examples of the substituent include the above-mentioned lower alkyl group, hydroxyl group, Examples thereof include a lower alkoxy group having 1 to 6 carbon atoms. The number of substituents on the benzene ring may be one or more.
【0009】R2は水素原子またはベンゼン環上に置換基
を有していてもよいフェニル基であって、置換基として
は上記R1で例示したものと同様のものが例示できる。R 2 is a hydrogen atom or a phenyl group which may have a substituent on the benzene ring, and examples of the substituent include those similar to those exemplified for R 1 above.
【0010】かかる光学活性フェネチルアミン誘導の体
具体例としては、1−フェニルエチルアミン、1−(4
−トリル)エチルアミン、N−ベンジル−1−フェニル
エチルアミン、N−(2−ヒドロキシ)ベンジル−1−
フェニルエチルアミン、N−(4−ヒドロキシ)ベンジ
ル−1−フェニルエチルアミン、N−(2−ヒドロキシ
−5−メトキシ)ベンジル−1−フェニルエチルアミ
ン、N−(3−ヒドロキシ−4−メトキシ)ベンジル−
1−フェニルエチルアミン、N−(4−ヒドロキシ−3
−メトキシ)ベンジル−1−フェニルエチルアミン、N
−(3−ヒドロキシ)ベンジル−1−(4−トリル)エ
チルアミン、N−(4−ヒドロキシ)ベンジル−1−
(4−トリル)エチルアミン、N−(3−エトキシ−4
−ヒドロキシ)ベンジル−1−(4−トリル)エチルア
ミン、1−フェニル−2−(4−トリル)エチルアミ
ン、N−ベンジル−1−フェニル−2−(4−トリル)
エチルアミン等のフェネチルアミン誘導体の光学活性体
が挙げられる。Specific examples of such an optically active phenethylamine derivative include 1-phenylethylamine and 1- (4
-Tolyl) ethylamine, N-benzyl-1-phenylethylamine, N- (2-hydroxy) benzyl-1-
Phenylethylamine, N- (4-hydroxy) benzyl-1-phenylethylamine, N- (2-hydroxy-5-methoxy) benzyl-1-phenylethylamine, N- (3-hydroxy-4-methoxy) benzyl-
1-phenylethylamine, N- (4-hydroxy-3
-Methoxy) benzyl-1-phenylethylamine, N
-(3-hydroxy) benzyl-1- (4-tolyl) ethylamine, N- (4-hydroxy) benzyl-1-
(4-tolyl) ethylamine, N- (3-ethoxy-4)
-Hydroxy) benzyl-1- (4-tolyl) ethylamine, 1-phenyl-2- (4-tolyl) ethylamine, N-benzyl-1-phenyl-2- (4-tolyl)
An optically active substance of a phenethylamine derivative such as ethylamine is exemplified.
【0011】これらの光学活性アミンのR体およびS体
を適宜選定することにより、上記一般式(2)で示され
る光学活性trans−シクロブタンジカルボン酸類と一般
式(3)で示される光学活性trans−シクロブタンジカ
ルボン酸類のうち所望の光学活性体を得ることが可能と
なる。By appropriately selecting the R-form and the S-form of these optically active amines, the optically active trans-cyclobutanedicarboxylic acids represented by the general formula (2) and the optically active trans-cyclobutanedicarboxylic acids represented by the general formula (3) are obtained. It is possible to obtain a desired optically active substance among cyclobutanedicarboxylic acids.
【0012】光学活性アミンの使用量は、収率の観点か
ら、一般式(1)でで示されるラセミ−trans−シクロ
ブタンジカルボン酸類に対して0.2倍以上が好ましく0.3
8モル倍以上がより好ましい。また得られる光学活性tra
ns−シクロブタンジカルボン酸類の光学純度の観点か
ら、一般式(1)で示されるラセミ−trans−シクロブ
タンジカルボン酸類に対して1.5モル倍以下が好まし
く、0.8モル倍以下がより好ましい。From the viewpoint of yield, the amount of the optically active amine used is preferably at least 0.2 times the racemic-trans-cyclobutanedicarboxylic acid represented by the general formula (1), more preferably 0.3 times.
It is more preferably at least 8 mol times. Also obtained optical activity tra
From the viewpoint of the optical purity of the ns-cyclobutanedicarboxylic acids, the molar ratio is preferably 1.5 mol times or less, more preferably 0.8 mol times or less, of the racemic-trans-cyclobutanedicarboxylic acids represented by the general formula (1).
【0013】上記一般式(1)でで示されるラセミ−tr
ans−シクロブタンジカルボン酸類と光学活性アミンに
よる塩形成反応は、通常、有機溶媒中で実施される。溶
媒の種類は、用いる光学活性アミンの種類により選択さ
れるが、通常、メタノール、エタノール、2−プロパノ
ール等のアルコール類、テトラヒドロフラン、ジオキサ
ン、t−ブチルメチルエーテル等のエーテル類またはこ
れらの混合溶媒が好ましく使用される。溶媒の使用量は
特に制限されないが、通常、上記一般式(1)で示され
るラセミ−trans−シクロブタンジカルボン酸類に対し
て通常、1〜50重量倍の範囲である。The racemic -tr represented by the above general formula (1)
The salt formation reaction between ans-cyclobutanedicarboxylic acids and an optically active amine is usually carried out in an organic solvent. The type of the solvent is selected according to the type of the optically active amine to be used, but usually, alcohols such as methanol, ethanol, and 2-propanol, tetrahydrofuran, dioxane, ethers such as t-butyl methyl ether, and a mixed solvent thereof are used. It is preferably used. The amount of the solvent to be used is not particularly limited, but is usually in the range of 1 to 50 times the weight of the racemic-trans-cyclobutanedicarboxylic acid represented by the general formula (1).
【0014】塩形成反応の反応温度は、通常、−20℃
以上、上述した用いる溶媒の沸点以下であり、好ましく
は0℃以上、溶媒の沸点より20℃低い温度の範囲であ
る。The reaction temperature of the salt formation reaction is usually -20 ° C.
As described above, the temperature is equal to or lower than the boiling point of the solvent used, preferably equal to or higher than 0 ° C and lower than the boiling point of the solvent by 20 ° C.
【0015】塩形成反応後、析出した結晶を例えば濾過
により溶液と分離し、この結晶を上記一般式(2)また
は(3)で示される光学活性trans−シクロブタンジカ
ルボン酸類を溶解しうる有機溶媒に溶解もしくは懸濁さ
せ、さらに塩酸もしくは硫酸等の水溶液を添加して光学
活性trans−シクロブタンジカルボン酸類と光学活性ア
ミンとの塩を分解することで目的とする光学活性trans
−シクロブタンジカルボン酸類を有機溶媒側に抽出する
ことができる。After the salt formation reaction, the precipitated crystals are separated from the solution by, for example, filtration, and the crystals are dissolved in an organic solvent capable of dissolving the optically active trans-cyclobutanedicarboxylic acid represented by the above general formula (2) or (3). Dissolve or suspend and further add aqueous solution such as hydrochloric acid or sulfuric acid to decompose the salt of optically active trans-cyclobutanedicarboxylic acid and optically active amine to obtain the desired optically active trans.
The cyclobutanedicarboxylic acids can be extracted to the organic solvent side;
【0016】この際、目的とするtrans−シクロブタン
ジカルボン酸類の抽出効率を向上させる目的で食塩等の
無機塩を添加するのも有効である。得られた光学活性tr
ans−シクロブタンジカルボン酸類の溶液から溶媒を留
去することで目的とする上光学活性trans−シクロブタ
ンジカルボン酸類を高収率で得ることができ、必要に応
じて再結晶等の操作を行うことでさらに精製することも
可能である。At this time, it is also effective to add an inorganic salt such as salt to improve the extraction efficiency of the intended trans-cyclobutanedicarboxylic acids. Obtained optical activity tr
By removing the solvent from the solution of ans-cyclobutanedicarboxylic acids, the desired optically active trans-cyclobutanedicarboxylic acids can be obtained in high yield, and further by performing operations such as recrystallization if necessary. Purification is also possible.
【0017】[0017]
【発明の効果】本発明の方法によれば、一般式(1)で
示されるラセミ−trans−シクロブタンジカルボン酸類
から光学活性アミンによる光学分割操作で一般式(2)
または(3)で示される光学活性trans−シクロブタン
ジカルボン酸類を高収率で取得することができる。According to the method of the present invention, the racemic-trans-cyclobutanedicarboxylic acid represented by the general formula (1) is subjected to an optical resolution operation using an optically active amine to obtain the general formula (2).
Alternatively, the optically active trans-cyclobutanedicarboxylic acids represented by (3) can be obtained in high yield.
【0018】[0018]
【実施例】以下、実施例により本発明をさらに詳細に説
明するが、本発明はこれにより限定されるものではな
い。EXAMPLES The present invention will be described in more detail with reference to the following Examples, but it should not be construed that the present invention is limited thereto.
【0019】(実施例1)(R)−N−(4−ヒドロキ
シ)ベンジル−1−フェニルエチルアミン116.8 mg
(0.514 mmol)およびt−ブチルメチルエーテル4.0
mLにラセミ体のtrans−1,1−ジエトキシシクロブタ
ン−2,3−ジカルボン酸209.5 mg(0.902 mmol)の
t−ブチルメチルエーテル溶液4.0 mLを室温で加え
た。室温で6日間放置し、生成した白色沈殿を濾過する
ことにより、(+)−trans−1,1−ジエトキシシク
ロブタン−2,3−ジカルボン酸の(R)−N−(4−ヒ
ドロキシ)ベンジル−1−フェニルエチルアミン塩を得
た(収率31.7%、72.3%ee)。Example 1 (R) -N- (4-hydroxy) benzyl-1-phenylethylamine 116.8 mg
(0.514 mmol) and t-butyl methyl ether 4.0
To mL, 4.0 mL of a t-butyl methyl ether solution of 209.5 mg (0.902 mmol) of racemic trans-1,1-diethoxycyclobutane-2,3-dicarboxylic acid was added at room temperature. The mixture was allowed to stand at room temperature for 6 days, and the formed white precipitate was filtered to obtain (R) -N- (4-hydroxy) benzyl of (+)-trans-1,1-diethoxycyclobutane-2,3-dicarboxylic acid. -1-Phenylethylamine salt was obtained (yield 31.7%, 72.3% ee).
【0020】(実施例2)実施例1と同様にして(R)
−N−(4−ヒドロキシ−3−メトキシ)ベンジル−1
−フェニルエチルアミン125.7 mg(0.488 mmol)を用
いることにより、ラセミ体のtrans−1,1−ジエトキ
シシクロブタン−2,3−ジカルボン酸217.2mg(0.90
mmol)より(+)−trans−1,1−ジエトキシシク
ロブタン−2,3−ジカルボン酸の(R)−N−(4−ヒ
ドロキシ−3−メトキシ)ベンジル−1−フェニルエチ
ルアミン塩を得た(収率27.0%、98.0%ee)。(Embodiment 2) In the same manner as in Embodiment 1, (R)
-N- (4-hydroxy-3-methoxy) benzyl-1
By using 125.7 mg (0.488 mmol) of -phenylethylamine, 217.2 mg (0.90 mg) of racemic trans-1,1-diethoxycyclobutane-2,3-dicarboxylic acid was used.
(mmol) to give (R) -N- (4-hydroxy-3-methoxy) benzyl-1-phenylethylamine salt of (+)-trans-1,1-diethoxycyclobutane-2,3-dicarboxylic acid. Yield 27.0%, 98.0% ee).
【0021】(実施例3)ラセミ体のtrans−1,1−
ジエトキシシクロブタン−2,3−ジカルボン酸898.4
mg(3.869 mmol)を2−プロパノール 3.5 mLに加
え、50℃に加熱し溶解させた。ここに(S)−N−(4
−ヒドロキシ)ベンジル−1−フェニルエチルアミン
395.1 mg(1.738 mmol)の2−プロパノール溶液 2.5
mLを50℃で加えた。室温で7日間放置し、生成した
白色沈殿を濾過することにより、(−)−trans−1,
1−ジエトキシシクロブタン−2,3−ジカルボン酸の
(S)−N−(4−ヒドロキシ)ベンジル−1−フェニル
エチルアミン塩(572.6 mg)を得た。この塩を1Nの水
酸化ナトリウム水溶液 10 mLで塩分解したのち、これ
をトルエン5 mLで2回抽出した。水層を塩酸でpH =1.
5とし、食塩で飽和させたのち酢酸エチル5 mLで3回抽
出した。酢酸エチル層をあわせて濃縮することにより
(−)−trans−1,1−ジエトキシシクロブタン−
2,3−ジカルボン酸を得た(収率32.2%、93.8%ee,
[α]D 25=−3.95°(c= 1.012,H2O))。(Example 3) racemic trans-1,1-
Diethoxycyclobutane-2,3-dicarboxylic acid 898.4
mg (3.869 mmol) was added to 3.5 mL of 2-propanol and heated to 50 ° C. to dissolve. Where (S) -N- (4
-Hydroxy) benzyl-1-phenylethylamine
395.1 mg (1.738 mmol) of 2-propanol solution 2.5
mL was added at 50 ° C. The mixture was allowed to stand at room temperature for 7 days, and the resulting white precipitate was filtered to obtain (-)-trans-1,
1-Diethoxycyclobutane-2,3-dicarboxylic acid (S) -N- (4-hydroxy) benzyl-1-phenylethylamine salt (572.6 mg) was obtained. The salt was hydrolyzed with 10 mL of a 1N aqueous solution of sodium hydroxide, and then extracted twice with 5 mL of toluene. The aqueous layer is pH = 1 with hydrochloric acid.
After saturating with sodium chloride, the mixture was extracted three times with 5 mL of ethyl acetate. The ethyl acetate layers are combined and concentrated to give (-)-trans-1,1-diethoxycyclobutane-
2,3-dicarboxylic acid was obtained (yield 32.2%, 93.8% ee,
[α] D 25 = −3.95 ° (c = 1.012, H 2 O)).
【0022】(実施例4)実施例3と同様にして(S)
−N−(4−ヒドロキ−3−メトキシ)ベンジル−1−
フェニルエチルアミン395.1 mg(1.738 mmol)を用い
ることにより、ラセミ体のtrans−1,1−ジエトキシ
シクロブタン−2,3−ジカルボン酸898.4 mg(3.869
mmol)より(−)− trans−1,1−ジエトキシシ
クロブタン−2,3−ジカルボン酸を得た(収率26.3
%、90.9%ee)。(Embodiment 4) In the same manner as in Embodiment 3, (S)
-N- (4-hydroxy-3-methoxy) benzyl-1-
By using 395.1 mg (1.738 mmol) of phenylethylamine, 898.4 mg (3.869 mg) of racemic trans-1,1-diethoxycyclobutane-2,3-dicarboxylic acid was used.
mmol), (-)-trans-1,1-diethoxycyclobutane-2,3-dicarboxylic acid was obtained (yield 26.3).
%, 90.9% ee).
Claims (2)
−trans−シクロブタンジカルボン酸類に光学活性アミ
ンを作用させていずれか一方のジアステレオマー塩を優
先的に析出させ、得られた塩を酸で分解することによる
一般式(2) (式中、Rは前記と同じである) または一般式(3) (式中、Rは前記と同じである)で示される光学活性tr
ans−シクロブタンジカルボン酸類の製造方法。1. The general formula (1) (Wherein, R represents a lower alkyl group) by reacting an optically active amine with a racemic-trans-cyclobutanedicarboxylic acid represented by the formula (1) to preferentially precipitate one of the diastereomeric salts. General formula (2) by decomposition with an acid (Wherein R is as defined above) or general formula (3) (Wherein R is as defined above)
A method for producing ans-cyclobutanedicarboxylic acids.
は、ベンゼン環上に置換基を有していてもよいベンジル
基を、R2は水素原子またはベンゼン環上に置換基を有し
ていてもよいフェニル基を、R3は水素原子またはメチル
基を示す。)で示される光学活性フェニルエチルアミン
誘導体である請求項1に記載の製造方法。2. An optically active amine of the general formula (4) (In the formula, * represents an asymmetric carbon atom. R 1 represents a hydrogen atom or a benzyl group which may have a substituent on a benzene ring, and R 2 represents a hydrogen atom or a substituent on a benzene ring. Wherein R 3 represents a hydrogen atom or a methyl group.) The optically active phenylethylamine derivative represented by the following formula:
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP35290797A JPH11180930A (en) | 1997-12-22 | 1997-12-22 | Production of optically active trans-cyclobutanedicarboxylic acids |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP35290797A JPH11180930A (en) | 1997-12-22 | 1997-12-22 | Production of optically active trans-cyclobutanedicarboxylic acids |
Publications (1)
Publication Number | Publication Date |
---|---|
JPH11180930A true JPH11180930A (en) | 1999-07-06 |
Family
ID=18427276
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP35290797A Pending JPH11180930A (en) | 1997-12-22 | 1997-12-22 | Production of optically active trans-cyclobutanedicarboxylic acids |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPH11180930A (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001106661A (en) * | 1999-08-04 | 2001-04-17 | Sumitomo Chem Co Ltd | Amine compound, intermediate, production method and reagent for optical resolution |
WO2002085833A1 (en) * | 2001-04-18 | 2002-10-31 | Kuraray Co., Ltd. | Processes for preparation of optically active 2-benzyl- succinic acid and optically active 2-benzylsuccinic acid monoamides |
JP2013522273A (en) * | 2010-03-16 | 2013-06-13 | ジヤンセン・フアーマシユーチカルズ・インコーポレーテツド | Methods and intermediates for the preparation of macrocyclic protease inhibitors of HCV |
CN109206311A (en) * | 2018-10-26 | 2019-01-15 | 山东谛爱生物技术有限公司 | A kind of preparation method of 3- oxo cyclobutane yl carboxylic acid |
-
1997
- 1997-12-22 JP JP35290797A patent/JPH11180930A/en active Pending
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001106661A (en) * | 1999-08-04 | 2001-04-17 | Sumitomo Chem Co Ltd | Amine compound, intermediate, production method and reagent for optical resolution |
WO2002085833A1 (en) * | 2001-04-18 | 2002-10-31 | Kuraray Co., Ltd. | Processes for preparation of optically active 2-benzyl- succinic acid and optically active 2-benzylsuccinic acid monoamides |
JP2013522273A (en) * | 2010-03-16 | 2013-06-13 | ジヤンセン・フアーマシユーチカルズ・インコーポレーテツド | Methods and intermediates for the preparation of macrocyclic protease inhibitors of HCV |
CN109206311A (en) * | 2018-10-26 | 2019-01-15 | 山东谛爱生物技术有限公司 | A kind of preparation method of 3- oxo cyclobutane yl carboxylic acid |
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