JPH0830057B2 - Process for producing 4-acetoxy-3-hydroxyethylazetidin-2-one derivative - Google Patents
Process for producing 4-acetoxy-3-hydroxyethylazetidin-2-one derivativeInfo
- Publication number
- JPH0830057B2 JPH0830057B2 JP61101856A JP10185686A JPH0830057B2 JP H0830057 B2 JPH0830057 B2 JP H0830057B2 JP 61101856 A JP61101856 A JP 61101856A JP 10185686 A JP10185686 A JP 10185686A JP H0830057 B2 JPH0830057 B2 JP H0830057B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- acetoxy
- reaction
- substituted pyridine
- production method
- 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.)
- Expired - Fee Related
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Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Description
【発明の詳細な説明】 （産業上の利用分野） 本発明は、３−位に水酸基が保護されたヒドロキシエ
チル基を有し、４−位にアセトキシ基を有する４−アセ
トキシ−３−ヒドロキシエチルアゼチジン−２−オン誘
導体の新規な製造方法に関する。DETAILED DESCRIPTION OF THE INVENTION Industrial Field of the Invention The present invention has 4-acetoxy-3-hydroxyethyl having a hydroxyethyl group having a hydroxyl group protected at the 3-position and an acetoxy group at the 4-position. The present invention relates to a novel method for producing an azetidin-2-one derivative.
４−アセトキシ−３−ヒドロキシエチルアゼチジン−
２−オン誘導体は、チエナマイシン等に代表されるカル
バペネム系β−ラクタム抗生物質や、ペネム系β−ラク
タム抗生物質の合成中間体として有用であることが知ら
れている〔たとえば、レイダー等、テトラヘドロン・レ
ターズ、23巻、2293頁（1982年）、およびヨシダ等、ケ
ミカル・アンド・フアーマシユテイカル・ブレチン（Ch
em.Pharm.Bull.）29巻,2899頁（1981年）〕。4-acetoxy-3-hydroxyethylazetidine-
The 2-one derivative is known to be useful as a carbapenem β-lactam antibiotic typified by thienamycin and a synthetic intermediate for a penem β-lactam antibiotic [for example, Raider, tetrahedron, etc.].・ Letters, Vol. 23, p. 2293 (1982), and Yoshida et al., Chemical and Pharmaceutical Bulletin (Ch
em.Pharm.Bull.) 29, 2899 (1981)].
（従来の技術と問題点） 従来、４−アセトキシ−３−ヒドロキシエチルアゼチ
ジン−２−オン誘導体の合成法として、６−アミノペニ
シラン酸から合成する方法〔ヨシダ等、Chem.Pharm.Bul
l.29巻,2899頁（1981年）〕、スレオニンから合成する
方法〔シオザキ等、テトラヘドロン、39巻、2399頁（19
83年）〕、アスパラギン酸から合成する方法〔レイダー
等、テトラヘドロン・レターズ、23巻、2293頁（1982
年）〕、β−ヒドロキシ酪酸のメタルエノレートから合
成する方法〔ナカイ等、ケミストリー・レターズ、1927
頁（1984年）〕等が知られている。しかし、いずれの方
法においても、β−ラクタム環の４−位にアセトキシ基
を導入するために、酢酸水銀、硫酸水銀等の水銀化合物
や四酢酸鉛等の工業的には好ましくない試薬を使用する
難点を有していた。(Conventional Technology and Problems) Conventionally, as a method for synthesizing a 4-acetoxy-3-hydroxyethylazetidin-2-one derivative, a method for synthesizing from 4-aminopenicillanic acid [Yoshida et al., Chem. Pharm.
29, 2899 (1981)], a method of synthesizing from threonine [Shiozaki et al., tetrahedron, 39, 2399 (19).
1983)], a method of synthesizing from aspartic acid [Raider et al., Tetrahedron Letters, 23, 2293 (1982)
)], A method of synthesizing β-hydroxybutyric acid from a metal enolate [Nakai et al., Chemistry Letters, 1927].
Page (1984)] etc. are known. However, in any method, in order to introduce an acetoxy group at the 4-position of the β-lactam ring, a mercury compound such as mercury acetate and mercury sulfate, or an industrially unfavorable reagent such as lead tetraacetate is used. It had some difficulties.
本発明者らは、３−位にＯ−保護ヒドロキシエチル
基、４−位にシリルエーテル基を有する新規なβ−ラク
タム化合物のＮ−保護体を用いて、４−位にアセトキシ
基を導入する製法を見出し、既に出願した（特開昭61-1
8758）。しかし、４−位にアセトキシ基を導入する際
に、β−ラクタムのＮに保護基を、あらかじめ導入し、
後で再度保護基を除去する操作が必要であつた。本発明
者等は、上記のＮの保護化を省略しても、４−位のアセ
トキシ化が一段で容易に達成できる条件を見出して、本
発明に至つた。以下に詳細を説明する。The present inventors introduce an acetoxy group at the 4-position by using an N-protected compound of a novel β-lactam compound having an O-protected hydroxyethyl group at the 3-position and a silyl ether group at the 4-position. A manufacturing method was found, and an application has already been filed (JP-A-61-1).
8758). However, when the acetoxy group is introduced at the 4-position, a protecting group is previously introduced at N of β-lactam,
It was necessary to remove the protecting group again later. The inventors of the present invention found the conditions under which the 4-position acetoxylation can be easily achieved even if the above N protection is omitted, and arrived at the present invention. The details will be described below.
（問題点を解決するための手段および作用効果） 本発明は、一般式（Ｉ） （式中、R1は水酸基の保護基、R2,R3,R4はC1〜C6の低級
アルキル基、フエニル基またはアラルキル基を示す）で
表わされるβ−ラクタム化合物に、有機溶媒中で0.2〜
３重量％の置換ピリジンの存在下で無水酢酸を作用させ
ることを特徴とする、一般式（II） （式中、R1は水酸基の保護基を示す）で表わされる４−
アセトキシ−３−ヒドロキシエチルアゼチジン−２−オ
ン誘導体の製造方法を要旨とする。(Means for Solving Problems and Actions and Effects) The present invention has the general formula (I) (Wherein R 1 represents a hydroxyl-protecting group, R 2 , R 3 and R 4 represent a C 1 to C 6 lower alkyl group, a phenyl group or an aralkyl group), and a β-lactam compound represented by an organic solvent 0.2 to
Acetic anhydride in the presence of 3% by weight of substituted pyridine, characterized by the general formula (II) (In the formula, R 1 represents a hydroxyl-protecting group)
The gist is a method for producing an acetoxy-3-hydroxyethylazetidin-2-one derivative.
一般式（Ｉ）で示される４−位にシリルエーテル基を
有するβ−ラクタム化合物は、本発明者らが既に出願
（特開昭61-18791）したように、反応式Ｉの方法によつ
て簡便に取得できる。The β-lactam compound represented by the general formula (I) having a silyl ether group at the 4-position can be prepared by the method of reaction formula I as already filed by the present inventors (JP-A 61-18791). Can be easily acquired.
反応式I: β−ラクタム化合物（Ｉ）の３−位のヒドロキシエチ
ル基のＯ−保護基であるR1としては、R1が一般式（II
I） （式中、R5,R6,R7はC1〜C6の低級アルキル基を示す）で
表わされるトリアルキルシリル基、たとえばtert−ブチ
ルジメチルシリル基、トリイソプロピルシリル基、イソ
プロピルジメチルシリル基、イソブチルジメチルシリル
基、ジメチル−1,1,2−トリメチルプロピルシリル基
や、その他ｔ−ブチル基、ベンジル基、トリクロロエト
キシカルボニル基、tert−ブトキシカルボニル基、ｐ−
ニトロベンジルオキシカルボニル基等が挙げられるが、
好ましくは反応中により安定であり、さらに酸処理によ
り選択的に脱保護されうるtert−ブチルジメチルシリル
基やイソプロピルジメチルシリル基やジメチル−1,1,2
−トリメチルプロピルシリル基がよい。又、β−ラクタ
ム化合物（Ｉ）のR2,R3,R4は、メチル、エチル、イソプ
ロピル、イソブチル、tert−ブチル、1,1,2−トリメチ
ルプロピル等のC1〜C6の低級アルキル基、フエニル基、
又はベンジル基、ｐ−ニトロベンジル基等のアラルキル
基から同一または異なつた基を選択できるが、好ましく
はR2＝R3＝R4＝メチルが最適である。Reaction formula I: As R 1 which is an O-protecting group for the hydroxyethyl group at the 3-position of the β-lactam compound (I), R 1 is represented by the general formula (II
I) (In the formula, R 5 , R 6 and R 7 represent a C 1 to C 6 lower alkyl group), for example, a tert-butyldimethylsilyl group, triisopropylsilyl group, isopropyldimethylsilyl group , Isobutyldimethylsilyl group, dimethyl-1,1,2-trimethylpropylsilyl group, and other t-butyl group, benzyl group, trichloroethoxycarbonyl group, tert-butoxycarbonyl group, p-
Examples include nitrobenzyloxycarbonyl group,
Preferably tert-butyldimethylsilyl group or isopropyldimethylsilyl group or dimethyl-1,1,2 which is more stable during the reaction and can be selectively deprotected by acid treatment.
-Trimethylpropylsilyl group is preferred. Further, R 2 , R 3 and R 4 of the β-lactam compound (I) are C 1 to C 6 lower alkyl such as methyl, ethyl, isopropyl, isobutyl, tert-butyl and 1,1,2-trimethylpropyl. Group, phenyl group,
Alternatively, the same or different groups can be selected from aralkyl groups such as a benzyl group and a p-nitrobenzyl group, but R 2 = R 3 = R 4 = methyl is most preferable.
上記のように調製した一般式（Ｉ） （式中、R1,R2,R3,R4は前記と同じ）で示されるβ−ラ
クタム化合物に、有機溶媒中、置換ピリジンの存在下、
無水酢酸を作用させて、目的の４−アセトキシ−３−ヒ
ドロキシエチルアゼチジン−２−オン誘導体（II） （式中、R1は前記と同じ）に変換するのであるが、この
際、置換ピリジンの反応系における濃度が、満足すべき
収率で化合物（II）を得るために、重要な因子であり、
最適な濃度範囲が存在する。General formula (I) prepared as described above (In the formula, R 1 , R 2 , R 3 and R 4 are the same as the above), in a β-lactam compound, in an organic solvent, in the presence of a substituted pyridine,
The desired 4-acetoxy-3-hydroxyethylazetidin-2-one derivative (II) is reacted with acetic anhydride. (Wherein R 1 is the same as above), and the concentration of the substituted pyridine in the reaction system is an important factor for obtaining the compound (II) in a satisfactory yield. ,
There is an optimal concentration range.
使用する置換ピリジンとしては、４−ジメチルアミノ
ピリジン、４−ジエチルアミノピリジン等のジアルキル
アミノピリジンや、４−ピロリジノピリジンや４−ピペ
リジノピリジン等の含窒素複素環基を置換基として有す
る置換ピリジンが好ましい。置換ピリジンの反応系にお
ける濃度は0.2〜３重量％の範囲が採用される。これよ
り低いと反応速度が低下し、基質の分解の副反応が多く
なり好ましくなく、濃度が高くなると下記の一般式（I
V）で示される副生物 （式中、R1は前記と同じ） の生成量が多くなり、満足すべき収率で目的の化合物
（II）を得ることはできない。無水酢酸の量は置換ピリ
ジンに対し少ないと反応速度が低下するため、置換ピリ
ジンに対し過剰量あればよく、好ましくは反応系におけ
る濃度が10〜50重量％の濃度の範囲で使用すればよい。Examples of the substituted pyridine used include dialkylaminopyridines such as 4-dimethylaminopyridine and 4-diethylaminopyridine, and substituted pyridines having a nitrogen-containing heterocyclic group such as 4-pyrrolidinopyridine and 4-piperidinopyridine as a substituent. Is preferred. The concentration of the substituted pyridine in the reaction system is 0.2 to 3% by weight. If it is lower than this, the reaction rate decreases, and side reactions of decomposition of the substrate increase, which is not preferable.
V) by-product (In the formula, R 1 is the same as the above), the production amount becomes large, and the target compound (II) cannot be obtained in a satisfactory yield. If the amount of acetic anhydride is smaller than that of the substituted pyridine, the reaction rate will decrease. Therefore, an excess amount of acetic anhydride may be used, and the concentration in the reaction system is preferably 10 to 50% by weight.
反応に使用する溶媒としては、塩化メチレンや四塩化
炭素等のハロゲン系溶媒、ｎ−ヘキサン等の炭化水素、
トルエン等の芳香族系炭化水素や、酢酸エチルやテトラ
ヒドロフランが好ましい。Examples of the solvent used in the reaction include halogen-based solvents such as methylene chloride and carbon tetrachloride, hydrocarbons such as n-hexane,
Aromatic hydrocarbons such as toluene, ethyl acetate and tetrahydrofuran are preferred.
反応温度は０℃〜−70℃の低温領域で実施することで
目的の化合物（II）を満足すべき収率で得ることができ
る。好ましくは、−10℃〜−50℃の温度条件下で反応を
おこなえばよい。By carrying out the reaction at a low temperature range of 0 ° C to -70 ° C, the desired compound (II) can be obtained in a satisfactory yield. Preferably, the reaction may be carried out under the temperature condition of -10 ° C to -50 ° C.
反応操作としては、塩化メチレンやトルエン等の有機
溶媒に、一般式（Ｉ）で示される４−位にシリルエーテ
ル基を有するβ−ラクタム化合物を溶解し、この溶液を
冷却し、この温度で無水酢酸および４−ジメチルアミノ
ピリジン等の置換ピリジンを一度に、あるいは分割して
加えて反応を行なう。反応経過を薄層クロマトグラフイ
ーでチエツクしながら実施し、原料は消失又は微量にな
つたところで、水へ反応液を注ぐ。次に有機層を炭酸水
素ナトリウム、水で洗浄した後、硫酸マグネシウムで乾
燥する。溶媒を留去して得られた粗結晶をｎ−ヘキサン
等の溶媒で再結晶することにより目的の４−アセトキシ
−３−ヒドロキシエチルアゼチジン−２−オン誘導体を
得る。又、溶媒を留去した反応混合物からカラムクロマ
トグラフイーにより４−アセトキシ−３−ヒドロキシエ
チルアゼチジン−２−オン誘導体を得ることもできる。As the reaction operation, a β-lactam compound having a silyl ether group at the 4-position represented by the general formula (I) is dissolved in an organic solvent such as methylene chloride or toluene, and the solution is cooled and dried at this temperature. The reaction is carried out by adding acetic acid and a substituted pyridine such as 4-dimethylaminopyridine all at once or in divided portions. The reaction progress is carried out while checking by thin layer chromatography, and when the raw material disappears or becomes a trace amount, the reaction solution is poured into water. Next, the organic layer is washed with sodium hydrogen carbonate and water and then dried over magnesium sulfate. The target 4-acetoxy-3-hydroxyethylazetidin-2-one derivative is obtained by recrystallizing the crude crystal obtained by distilling off the solvent, with a solvent such as n-hexane. Alternatively, the 4-acetoxy-3-hydroxyethylazetidin-2-one derivative can be obtained by column chromatography from the reaction mixture obtained by removing the solvent.
（実施例） 以下実施例で本発明を詳しく説明するが、これらの実
施例によつて本発明が限定されるものではない。(Examples) Hereinafter, the present invention will be described in detail with reference to Examples, but the present invention is not limited to these Examples.
実施例１ （3R,4R）−４−アセトキシ−３−〔（Ｒ）−１−ter
t−ブチルジメチルシリロキシエチル〕アゼチジン−２
−オンの合成 （3R,4R）−３−〔（Ｒ）−１−tert−ブチルジメチ
ルシリロキシエチル〕−４−トリメチルシリロキシアゼ
チジン−２−オン 157mgを塩化メチレン0.9mlに溶解
し、これを−35℃に冷却した。ついで544mgの無水酢酸
を添加し、さらに20mgの４−ジメチルアミノピリジンを
添加して、−35℃で１昼夜攪拌した。反応後、５％NaHC
O3水溶液を加え分液し、水で有機層を洗浄し、硫酸マグ
ネシウムで乾燥後、溶媒を減圧留去してワツクス状固体
147mgを得た。Example 1 (3R, 4R) -4-acetoxy-3-[(R) -1-ter
t-Butyldimethylsilyloxyethyl] azetidine-2
Synthesis of 3-one (3R, 4R) -3-[(R) -1-tert-butyldimethylsilyloxyethyl] -4-trimethylsilyloxyazetidin-2-one 157 mg was dissolved in 0.9 ml methylene chloride. Was cooled to -35 ° C. Then, 544 mg of acetic anhydride was added, further 20 mg of 4-dimethylaminopyridine was added, and the mixture was stirred at -35 ° C for one day. After reaction, 5% NaHC
An aqueous O 3 solution was added for liquid separation, the organic layer was washed with water, dried over magnesium sulfate, and the solvent was distilled off under reduced pressure to give a wax-like solid.
147 mg was obtained.
反応混合物を高速液体カラムクロマトグラフイー（カ
ラムYMC−パツク（Ａ−303 ODS）4.6×250mm,カラム温
度50℃，溶媒メタノール：水＝7:3（v/v）、流量1ml/
分，検出210nm）で分析すると、72.5mgの（3R,4R）−４
−アセトキシ−３−〔（Ｒ）−１−tert−ブチルジメチ
ルシリロキシエチル〕アゼチジン−２−オンが生成して
いた。High-performance liquid column chromatography (column YMC-pack (A-303 ODS) 4.6 × 250 mm, column temperature 50 ° C., solvent methanol: water = 7: 3 (v / v), flow rate 1 ml /
Min, detection 210nm), 72.5mg of (3R, 4R) -4
-Acetoxy-3-[(R) -1-tert-butyldimethylsilyloxyethyl] azetidin-2-one had formed.
さらにこの反応混合物をｎ−ヘキサンに溶解し、不溶
物を過後、−15℃で冷却放置すると、44mgの白色固体
が得られ、以下の物性値から、目的の（3R,4R）−４−
アセトキシ−３−〔（Ｒ）−１−tert−ブチルジメチル
シリロキシエチル〕アゼチジン−２−オンであることが
確認された。Further, this reaction mixture was dissolved in n-hexane, and after insoluble matter was passed through it, the mixture was allowed to cool and stand at -15 ° C to obtain 44 mg of a white solid. From the following physical properties, the desired (3R, 4R) -4-
It was confirmed to be acetoxy-3-[(R) -1-tert-butyldimethylsilyloxyethyl] azetidin-2-one.
〔α〕25＝＋50°（ｃ＝0.5,CHCl3）， mp:107〜108℃1 H‐NMR（90MHz,CDCl3），δ（ppm）： 0.08（6H,s）,0.84（9H,s）,1.20（3H,d）,2.10（3H,
s）,3.04（1H,dd）,4.12（1H,m）,5.76（1H,d）,6.73
（NH） 実施例２ （3R,4R）−４−アセトキシ−３−〔（Ｒ）−１−ter
t−ブチルジメチルシリロキシエチル〕アゼチジン−２
−オンの合成 （3R,4R）−３−〔（Ｒ）−１−tert−ブチルジメチ
ルシリロキシエチル〕−４−トリメチルシリロキシアゼ
チジン−２−オン 156mgを3.6mlのトルエンに溶解し、
−35℃に冷却後、782mgの無水酢酸および30mgの４−ジ
メチルアミノピリジンを添加し、43時間−35℃で攪拌を
おこなつた。反応後、実施例１と同様の方法で処理を
し、高速液体クロマトグラフイー分析したところ、（3
R,4R）−４−アセトキシ−３−〔（Ｒ）−１−tert−ブ
チルジメチルシリロキシエチル〕アゼチジン−２−オン
が72mg生成していた。[Α] 25 = + 50 ° (c = 0.5, CHCl 3 ), mp: 107-108 ° C. 1 H-NMR (90 MHz, CDCl 3 ), δ (ppm): 0.08 (6H, s), 0.84 (9H, s ), 1.20 (3H, d), 2.10 (3H, d)
s), 3.04 (1H, dd), 4.12 (1H, m), 5.76 (1H, d), 6.73
(NH) Example 2 (3R, 4R) -4-acetoxy-3-[(R) -1-ter
t-Butyldimethylsilyloxyethyl] azetidine-2
Synthesis of 3-one (3R, 4R) -3-[(R) -1-tert-butyldimethylsilyloxyethyl] -4-trimethylsilyloxyazetidin-2-one 156 mg was dissolved in 3.6 ml toluene,
After cooling to -35 ° C, 782 mg of acetic anhydride and 30 mg of 4-dimethylaminopyridine were added, and the mixture was stirred for 43 hours at -35 ° C. After the reaction, the same treatment as in Example 1 was carried out, and high performance liquid chromatography analysis revealed that (3
72 mg of R, 4R) -4-acetoxy-3-[(R) -1-tert-butyldimethylsilyloxyethyl] azetidin-2-one was formed.
反応物をシリカゲルクロマトグラフイー（ヘキサン：
酢酸エチル＝10:1）に付し、（3R,4R）−４−アセトキ
シ−３−〔（Ｒ）−１−tert−ブチルジメチルシリロキ
シエチル〕アゼチジン−２−オン 65mgを針状結晶とし
て得た。The reaction product was subjected to silica gel chromatography (hexane:
Ethyl acetate = 10: 1) to give (3R, 4R) -4-acetoxy-3-[(R) -1-tert-butyldimethylsilyloxyethyl] azetidin-2-one as a needle crystal (65 mg). It was
実施例３ （3R,4R）−４−アセトキシ−３−〔（Ｒ）−１−ter
t−ブチルジメチルシリロキシエチル〕アゼチジン−２
−オンの合成 （3R,4R）−３−〔（Ｒ）−１−tert−ブチルジメチ
ルシリロキシエチル〕−４−トリメチルシリロキシアゼ
チジン−２−オンを原料として、反応系の４−ジメチル
アミノピリジン,4−ピロリジノピリジンの濃度を変化さ
せて反応をおこない、（3R,4R）−４−アセトキシ−３
−〔（Ｒ）−１−tert−ブチルジメチルシリロキシエチ
ル〕アゼチジン−２−オンの生成収率を実施例１と同様
に、高速液体クロマトグラフイーで分析した。Example 3 (3R, 4R) -4-acetoxy-3-[(R) -1-ter
t-Butyldimethylsilyloxyethyl] azetidine-2
Synthesis of 3-one Using (3R, 4R) -3-[(R) -1-tert-butyldimethylsilyloxyethyl] -4-trimethylsilyloxyazetidin-2-one as a starting material, 4-dimethylamino The reaction was carried out by changing the concentrations of pyridine and 4-pyrrolidinopyridine to give (3R, 4R) -4-acetoxy-3.
The production yield of-[(R) -1-tert-butyldimethylsilyloxyethyl] azetidin-2-one was analyzed by high performance liquid chromatography in the same manner as in Example 1.
結果を表１に示した。The results are shown in Table 1.
実施例４ 各種の４−アルキルシリロキシアゼチジン−２−オン
（化合物Ａ）を原料として実施例１と同一の方法で得ら
れる４−アセトキシアゼチジン−２−オン（化合物Ｂ）
の生成収率を表２に示した。 Example 4 4-acetoxyazetidin-2-one (Compound B) obtained by the same method as in Example 1 using various 4-alkylsilyloxyazetidin-2-ones (Compound A) as raw materials
The production yield of is shown in Table 2.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 大橋 武久 兵庫県神戸市灘区篠原伯母野山町３−９− 14 (72)発明者 渡辺 清 兵庫県明石市松ケ丘５丁目15の41 (56)参考文献 特開 昭61−18758（ＪＰ，Ａ) ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Takehisa Ohashi 3-9-14, Noboru Shinohara, Nada-ku, Nada-ku, Kobe-shi, Hyogo (72) Inventor Kiyoshi Watanabe 5-15, Matsugaoka, Akashi-shi, Hyogo (56) Reference Reference JP-A-61-18758 (JP, A)
Claims (9)
アルキル基、フェニル基またはアラルキル基を示す。） で表わされるβ−ラクタム化合物に、有機溶媒中で0.2
〜３重量％の置換ピリジンの存在下で、無水酢酸を作用
させることを特徴とする、一般式（II） （式中、R1は水酸基の保護基を示す） で表わされる４−アセトキシ−３−ヒドロキシエチルア
ゼチジン−２−オン誘導体の製造方法。1. A general formula (I) (Wherein R 1 represents a hydroxyl-protecting group, R 2 , R 3 and R 4 represent a C 1 to C 6 lower alkyl group, a phenyl group or an aralkyl group). 0.2 in solvent
General formula (II), characterized in that acetic anhydride is allowed to act in the presence of ~ 3% by weight of substituted pyridine. (In the formula, R 1 represents a hydroxyl-protecting group.) A method for producing a 4-acetoxy-3-hydroxyethylazetidin-2-one derivative represented by the formula:
ある特許請求の範囲第１項記載の製造方法。2. R 1 is a general formula (III). (Wherein R 5 , R 6 , and R 7 represent a C 1 to C 6 lower alkyl group), and the production method according to claim 1.
許請求の範囲第１項記載の製造方法。3. The production method according to claim 1, wherein R 1 is a t-butyldimethylsilyl group.
特許請求の範囲第１項記載の製造方法。4. The production method according to claim 1, wherein R 1 is an isopropyldimethylsilyl group.
ルシリル基である特許請求の範囲第１項記載の製造方
法。5. The method according to claim 1, wherein R 1 is a dimethyl-1,1,2-trimethylpropylsilyl group.
第１項記載の製造方法。6. The production method according to claim 1, wherein R 2 , R 3 and R 4 are methyl groups.
ンである特許請求の範囲第１項記載の製造方法。7. The production method according to claim 1, wherein the substituted pyridine is 4-dimethylaminopyridine.
ある特許請求の範囲第１項記載の製造方法。8. The process according to claim 1, wherein the substituted pyridine is 4-pyrrolidinopyridine.
ある特許請求の範囲第１項記載の製造方法。9. The method according to claim 1, wherein the substituted pyridine is 4-piperidinopyridine.
Priority Applications (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61101856A JPH0830057B2 (en) | 1986-04-30 | 1986-04-30 | Process for producing 4-acetoxy-3-hydroxyethylazetidin-2-one derivative |
| CA000535802A CA1256444A (en) | 1986-04-30 | 1987-04-28 | Process for preparing 4-acetoxy-3- hydroxyethylazetidin-2-one derivatives |
| AU72140/87A AU601180B2 (en) | 1986-04-30 | 1987-04-28 | Process for preparing 4-acetoxy-3-hydroxyethylazetidin -2- one derivatives |
| EP87106234A EP0247378B1 (en) | 1986-04-30 | 1987-04-29 | Process for preparing 4-acetoxy-3-hydroxyethylazetidin-2-one derivatives |
| ES87106234T ES2017956B3 (en) | 1986-04-30 | 1987-04-29 | PROCEDURE FOR PREPARING DERIVATIVES OF 4-ACETOXI-3-HIDROXIETILAZETIDIN-2-ONA. |
| DE8787106234T DE3765009D1 (en) | 1986-04-30 | 1987-04-29 | METHOD FOR PRODUCING 4-ACETOXY-3-HYDROXYAETHYL-AZETIDINE-2-ONE DERIVATIVES. |
| KR1019870004232A KR910003612B1 (en) | 1986-04-30 | 1987-04-30 | Process for preparing 4-acetoxy-3-hydroxyethylazetidin-2-one derivatives |
| US07/309,935 US4914200A (en) | 1986-04-30 | 1989-02-14 | Process for preparing 4-acetoxy-3-hydroxyethylazetidin-2-one derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61101856A JPH0830057B2 (en) | 1986-04-30 | 1986-04-30 | Process for producing 4-acetoxy-3-hydroxyethylazetidin-2-one derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62258353A JPS62258353A (en) | 1987-11-10 |
| JPH0830057B2 true JPH0830057B2 (en) | 1996-03-27 |
Family
ID=14311667
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61101856A Expired - Fee Related JPH0830057B2 (en) | 1986-04-30 | 1986-04-30 | Process for producing 4-acetoxy-3-hydroxyethylazetidin-2-one derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0830057B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPWO2007142207A1 (en) * | 2006-06-06 | 2009-10-22 | 株式会社カネカ | Process for producing 4-substituted azetidinone derivatives |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6118758A (en) * | 1985-01-14 | 1986-01-27 | Kanegafuchi Chem Ind Co Ltd | Preparation of 4-acetoxy-hydroxyethylacetidin-2-one derivative |
-
1986
- 1986-04-30 JP JP61101856A patent/JPH0830057B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JPS62258353A (en) | 1987-11-10 |
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