WO2003080571A1 - Procede de production de composes azetidinone - Google Patents

Procede de production de composes azetidinone Download PDF

Info

Publication number
WO2003080571A1
WO2003080571A1 PCT/JP2003/001615 JP0301615W WO03080571A1 WO 2003080571 A1 WO2003080571 A1 WO 2003080571A1 JP 0301615 W JP0301615 W JP 0301615W WO 03080571 A1 WO03080571 A1 WO 03080571A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
metal atom
periodic table
general formula
production method
Prior art date
Application number
PCT/JP2003/001615
Other languages
English (en)
Japanese (ja)
Inventor
Takaji Matsumoto
Toshiyuki Murayama
Takashi Moroi
Original Assignee
Takasago International Corporation
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Takasago International Corporation filed Critical Takasago International Corporation
Priority to KR10-2004-7008611A priority Critical patent/KR20040095198A/ko
Priority to AU2003211227A priority patent/AU2003211227A1/en
Publication of WO2003080571A1 publication Critical patent/WO2003080571A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
    • 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

Definitions

  • the present invention relates to a method for producing an azetidinone compound which is an important synthetic intermediate for a compound of the present invention.
  • R represents an alkyl group, a benzyl group which may have a substituent, or an aryl group which may have a substituent.
  • Examples of the production method include the following reaction scheme 1 described in JP-A-57-123182.
  • An object of the present invention is to solve the problems of the conventional method as described above: a desired intermediate for the synthesis of a potent antibacterial agent having a methyl group at the 1'-3 position can be prepared under a mild condition under a short condition. It is an object of the present invention to provide a method for obtaining a compound with good yield in a process and selectively.
  • the present invention has the following general formula [2]
  • R 2 represents a hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms
  • R 3 represents an alkyl group having 1 to 12 carbon atoms, a phenyl group which may have a substituent
  • X represents an oxygen atom or a sulfur atom Represents.
  • M represents a metal atom
  • Y represents a halogen atom
  • R 4 has a lower alkyl group having 1 to 4 carbon atoms, a lower alkoxy group having 1 to 4 carbon atoms, and may have a substituent.
  • Good phenoxy, alkylsulfonyldioxy, arylsulfonyldioxy, alkylsulfonyloxy, 7-ylsulfonyloxy grave, cyclopentenyl, or pentamethylcyclopentenyl
  • n and m are integers from 0 to 4, and n + m is the valence of M.
  • the present invention does not require the conversion of a diazo compound into a silyl enol ether, and allows the compound represented by the general formula [2] and the diazo compound represented by the general formula [3] to be present in the presence of a specific metal compound and a base.
  • An object of the present invention is to provide a method for selectively producing a azetidinone compound having a desired 1'-1] 3 configuration under mild conditions in a short step with good yield simply by reacting under the following conditions.
  • examples of the hydroxyl-protecting group represented by R 1 include, for example, those commonly used in the field of peptide chemistry and] 3-lactam compounds. All of the hydroxyl protecting groups used are mentioned.
  • trimethylsilyl group triethylsilyl group, triisopropylsilyl group, dimethylisopropylsilyl group, getylisopropylsilyl group, dimethyl (2,3-dimethyl-2-butyl) silyl group, tert-butyldimethylsilyl group, dimethyl Trees having 1 to 6 alkylsilyl groups such as xylsilyl groups, for example di-carbons having 1 to 6 alkyl-carbon atoms having 6 to 18 arylsilyl groups such as dimethylcumylsilyl group, for example, tert-butyldiphene 6 to 18 aryl carbons such as erucyl and diphenylmethylsilyl groups—1 to 6 alkylsilyl groups such as triphenylsilyl group and tricarbons such as triphenylsilyl group and 6 to 18 aryl silyl groups such as tri Tri-carbon number such as
  • Tri-substituted silyl group such as aralkylsilyl group; for example, benzyl group, 4-methoxybenzyl group, 2-ditrobenzyl group, 412-trobenzyl group, diphenylmethyl group, triphenylmethyl group, etc.
  • aralkyloxycarbonyl groups having 7 to 19 carbon atoms for example, benzyloxycarbonyl group, 4-nitrobenzyloxycarbonyl group, etc.
  • carbon atoms having 2 to 19 carbon atoms for example, aralkyloxycarbonyl groups having 7 to 19 carbon atoms (for example, benzyloxycarbonyl group, 4-nitrobenzyloxycarbonyl group, etc.), and carbon atoms having 2 to 19 carbon atoms.
  • An alkenyloxylponyl group e.g., a 7-lyloxycarbonyl group
  • a tri-C1-6alkylsilyl group e.g., a tri-C1-6alkylsilyl group
  • more preferably a tert-butyldimethylsilyl group can be
  • Examples of the leaving group represented by L include, for example, an acyloxy group (for example, an alkoxyyloxy group, an aryloxy group, an arylalkanoyloxy group, an alkylsulfonyloxy group, an arylsulfonyloxy group, an alkoxycarbonyl group)
  • an alkanoylthio group an aroylthio group, an alkylthio group, an arylthio group, an alkylsulfinyl group
  • Examples thereof include a arylsulfinyl group, an alkylsulfonyl group, an arylsulfonyl group, and a halogen atom.
  • L is an alkanoyloxy group
  • specific examples include an acetooxy group, a propionyloxy group, a ptyryloxy group, an ⁇ -fluoroacetoxy group, an ⁇ -chloroacetoxy group, an ⁇ -promoacetoxy group, an ⁇ - A straight chain which may be substituted with 1 to 3 substituents such as halogen atoms, cyano groups, etc.
  • Alkanoyloxy group such as 1-doacetoxy group, ⁇ , difluoroacetoxy group, ⁇ , dichloroacetoxy group, and cyanoacetoxy group;
  • Alkanoyloxy group isoptyryloxy group, cyclohexyl carbonyloxy P Examples include branched or cyclic alkanoyloxy groups such as 15 groups.
  • L is an aryloxy group
  • specific examples include a monocyclic or polycyclic ring such as a benzoyloxy group, a 1-naphthoyloxy group, a 2-naphthyloxy group, a nicotinyloxy group, an isonicotinoyloxy group, and a fluorfluorooxy group.
  • L is an arylalkanoyloxy group
  • arylalkanoyloxy group examples include a phenylacetoxy group and the like.
  • L is an alkylsulfonyloxy group
  • specific examples include a methanesulfonyloxy group, an ethanesulfonyloxy group, a propanesulfonyloxy group, and a trifluorosulfonyl methanesulfonyloxy group.
  • L is an arylsulfonyloxy group
  • specific examples include a benzenesulfonyloxy group and a p-toluenesulfonyloxy group.
  • L is an alkoxycarbonyloxy group
  • specific examples include a methoxycarbonyloxy group and an ethoxycarbonyloxy group.
  • L is an aralkoxycarbonyloxy group
  • specific examples include a benzyloxycarbonyloxy group and the like.
  • L is an alkoxyalkyl group
  • specific examples include a methoxyacetoxy group and an ethoxyacetoxy group.
  • L is a carbamoyloxy group
  • specific examples include an N-methylcarbamoyl group.
  • L is an alkanoylthio group
  • specific examples include an acetylthio group and a propionylthio group.
  • L is an arylothio group
  • specific examples include a benzoylthio group and a naphthoylthio group.
  • L is an alkylthio group
  • specific examples include a methylthio group, an ethylthio group, an n-propylthio group, an isopropylthio group, an n-butylthio group, an isobutylthio group, a tert-butylthio group, and the like.
  • L is an arylthio group
  • specific examples include a phenylthio group and a naphthylthio group. 1615 groups and the like.
  • L is an alkylsulfinyl group
  • specific examples include a methanesulfinyl group, a benzenesulfinyl group, an n-propanesulfenyl group, and an n-butanesulfinyl group.
  • L is an arylsulfinyl group
  • specific examples include a benzenesulfinyl group and a p-toluenesulfinyl group.
  • L is an alkylsulfonyl group
  • specific examples include a methanesulfonyl group, an ethanesulfonyl group, an n-propanesulfonyl group, and an n-butanesulfonyl group.
  • L is an arylsulfonyl group
  • specific examples include a benzenesulfonyl group and a p-toluenesulfonyl group.
  • L is a halogen atom
  • specific examples include fluorine, chlorine, bromine, iodine and the like.
  • these leaving groups particularly preferred are an acetoxyl group and the like.
  • specific examples of the lower alkyl group having 1 to 4 carbon atoms represented by R 2 include a methyl group and an ethyl group.
  • Preferred R 2 is a hydrogen atom or a methyl group.
  • alkyl group having 1 to 12 carbon atoms represented by R 3 include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, Examples include an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, a nonyl group, a decyl group, a decyl group and a dodecyl group.
  • alkenyl group having 2 to 5 carbon atoms represented by R 3 include, for example, a bier group, an aryl group, a 1-propenyl group, an isopropyl group, a 1-butenyl group, a 2-butenyl group, 2-methylaryl group and the like.
  • Examples of the substituent of the phenyl group which may have a substituent represented by R 3 include, for example, 5 Lower alkyl groups having 1 to 4 carbon atoms, lower alkoxy groups having 1 to 4 carbon atoms, nitro groups, and haptogen atoms.
  • the lower alkyl group having 1 to 4 carbon atoms as a substituent include, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, te It—butyl group and the like.
  • Specific examples of the lower alkoxy group having 1 to 4 carbon atoms include, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert- Butoxy group and the like.
  • specific examples of the halogen atom include, for example, fluorine, chlorine, bromine, and iodine.
  • examples of the substituent of the aralkyl group having 7 to 15 carbon atoms include a lower alkyl group having 1 to 4 carbon atoms and a lower alkyl group having 1 to 4 carbon atoms. And a nitro group, a nitro group and a halogen atom.
  • lower alkyl group having 1 to 4 carbon atoms as a substituent include, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group and the like.
  • lower alkoxy groups having 1 to 4 carbon atoms include, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec butoxy, tert-butoxy.
  • halogen atom include, for example, fluorine, chlorine, bromine, and iodine.
  • aralkyl group having a carbon number of 7 to 15 even if it has a substituent include a benzyl group, a para-phenyl group, a 3-phenyl group, a ⁇ -phenyl group, and a ⁇ -phenyl group.
  • a benzyl group, a para-phenyl group, a 3-phenyl group, a ⁇ -phenyl group, and a ⁇ -phenyl group include a benzyl group, a para-phenyl group, a 3-phenyl group, a ⁇ -phenyl group, and a ⁇ -phenyl group.
  • the 5- to 8-membered alicyclic group which may have a substituent represented by R 3 include a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group and the like.
  • the substituent include a lower alkyl group having 1 to 4 carbon atoms such as a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group and a tert-butyl group.
  • R 3 is lower alkyl having 1 to 4 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, and tert-butyl.
  • 01615 kill group aralkyl having 7 to 15 carbon atoms which may have a substituent such as a benzyl group, a p-nitrobenzyl group, or a p-methoxybenzyl group (nitro group, methoxy group, etc.)
  • the metal atom represented by M is, for example, commonly used in organic synthetic chemistry, carbon-carbon bond formation reaction, and the like.
  • metals of Group 4 of the periodic table by IUPAC such as titanium and zirconium
  • metals of Group 14 of the periodic table by IUPAC such as gayne and tin
  • Metals of Group 1 and 3 of the Periodic Table by IUPAC such as boron and aluminum
  • scandium, yttrium, lanthanides lanthanum, cerium, praseodymium, neodymium, samaridium, gadolinium, dysprosium, erbium, ytterbium, etc.
  • Group 3 metals Periodic table metals such as iron and ruthenium
  • Groups 8 metals The first Group II metal such as Table and the like.
  • examples of the halogen atom represented by Y include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
  • specific examples of the lower alkyl group having 1 to 4 carbon atoms represented by R 4 include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group and an isobutyl group. , Sec-butyl group, tert-butyl group and the like.
  • Specific examples of the lower alkoxy group having 1 to 4 carbon atoms include, for example, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, Examples thereof include n-butoxy group, isobutoxy group, sec-butoxy group, tert-butoxy group and the like.
  • Examples of the substituent of the phenoxy group which may have a substituent represented by R 4 include a lower alkyl group having 1 to 4 carbon atoms, a lower alkoxy group having 1 to 4 carbon atoms, and a halogen atom. And the like.
  • specific examples of the lower alkyl group having 1 to 4 carbon atoms as a substituent include, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isopropyl group, sec-butyl group, tert-butyl group and the like.
  • Specific examples of the lower alkoxy group having 1 to 4 carbon atoms include, for example, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, sec-butoxy group, tert-butoxy group, and the like.
  • examples of the halogen atom include fluorine, chlorine, bromine, and iodine. And the like.
  • alkylsulfonyldioxy group represented by R 4 include, for example, a methanesulfonyldioxy group, an ethanesulfonyldioxy group, and a trifluoromethanesulfonyldioxy group.
  • arylsulfonyldioxy group represented by R 4 include, for example, a benzenesulfonyldioxy group and a p-toluenesulfonyldioxy group.
  • alkylsulfonyloxy group represented by R 4 include, for example, a methanesulfonyloxy group, an ethanesulfonyloxy group, and a trifluoromethanesulfonyloxy group.
  • arylsulfonyloxy group represented by R 4 include, for example, a benzenesulfonyloxy group and a p-toluenesulfonyloxy group.
  • the method for producing the compound represented by the general formula [2] is not particularly limited thereto.
  • the method for producing the diazo compound represented by the general formula [3] is not particularly limited, and examples thereof include, for example, JP-A-58-103358, JP-A-61
  • the compound can be synthesized by the method described in Japanese Patent Application Laid-Open No. 2752528 or a method analogous thereto.
  • diazo compound represented by the general formula [3] include, for example,
  • azo compounds more preferred are, for example,
  • Aryl 2-diazo 1-3-oxopen can be mentioned.
  • metal compound represented by the general formula [4] used in the present invention a commercially available product may be used as it is, or it may be purified and used as needed.
  • the metal compound represented by the general formula [4] for example, T i C 1 4, T i C 1 (OCH 3), T i C 1 (OC 3 H 5), T i C "(O - n - P r), T i C 1 (O- i - P r), T i C 1 (OB u), T i C 1 3 (O - i - B u),
  • S n IS n (OSOCF 3) tin compounds such as 2; F e C l 3, F e B r 3, iron compounds such as F e I 3; (C 2 H 5) 2O - BF (CH 3) 2 BOS 0 2 CF 3 , (C 2 H 5 ) 2 BOSO 2 CF (Pr) 2 BOS 0 2 CF 3 , (Bu) 2 BOS 0 2 CF 3, etc .; boron compounds; (CH 3 ) Si OSOCF (Silicon compounds such as CH 3 S i Cl; S c F 3 , S c C 1 S c Br 3 , S cl 3 , S c (O i -P r) 3 , S c
  • (OSO 2 CH 3) erbium compounds such as 3; Y b F 3, Y b C l 3, Yb B r 3, Y Ytterbium compounds such as PC Lanto 15 b I 3 , Y b ( ⁇ i-i-Pr) 3 , Y b (OSO 2 CH 3 ) 3 and the like.
  • C p represents a cyclopentagenenyl group
  • C p * represents a pentamethylcyclopentenyl group
  • T i C 1 4 (four titanium emissions chloride), Z n CI 2 (zinc dichloride), Z r C 1 4 (zirconium tetrachloride), A 1 C 1 ( aluminum trichloride), S n C 1 4 (tin tetrachloride), (C 2 H 5) 2 0 'BF 3 ( boron trifluoride etherate), (CH 3) SOS 0 2 CF ( Torimechirushi Rirutori Fuller g) , (CH 3 ) 3 SiC 1 (trimethylsilyl chloride) and the like.
  • These metal compounds may be used alone or in an appropriate combination of two or more.
  • Examples of the base used in the production method of the present invention include primary amines, secondary amines, tertiary amines, and pyridines.
  • the base is a primary amine
  • the base is a primary amine
  • examples when the base is a primary amine include, for example, ethylamine, propylamine, butyramine, aniline, benzylamine and the like.
  • the base is a secondary amine
  • the base is a secondary amine
  • examples of the case where the base is a secondary amine include, for example, getylamine, di-n-propylamine, diisopropylamine, methylisopropylamine, ethylisopropylamine, di-n-butylamine, diisobutylamine, di-sec— Butylamine, ditert-butylamine, N-methylaniline, N-ethylaniline, pyrrolidine, piperidine, morpholin, piperazine, imidazole, dibenzylamine, and the like.
  • the base is a tertiary amine
  • specific examples include trimethylamine, triethylamine, tripropylamine, triisopropylamine, diisopropylmethylamine, diisopropylethylamine, tri-n-butylamine, tribenzylamine, and N-methyl.
  • the base is a pyridine
  • specific examples include pyridine, ⁇ -picolin, i3-picoline, apicolin, 2,6-lutidine, 2-ethylpyridin, 3-ethylpyridine, 4-ethylpyridin, N, N—
  • Examples include dimethylamino pyridine, quinoline, and isoquinoline.
  • bases for example, triethylamine, tri-n-butylethylamine, diisopropylethylamine, N-methylpiperidine, N-ethylpiperidine, N-methylmorpholin, N-ethylmorpholin, 1,5-diazabicyclo [4.3.0] — 5—Nonene, 1,8-diazabicyclo [5.4.0] — 7-Dindecene, 1,4 diazabicyclo [2.2.2] octane, N, N-dimethylamino pyridine, etc. Is more preferred because of its versatility and high reaction selectivity and yield.
  • bases may be used alone or in combination of two or more.
  • a commercially available product may be used as it is, or may be purified and used as needed.
  • any solvent may be used as long as it is an inert solvent that does not participate in the reaction.
  • hydrocarbon solvents such as pentane, hexane, and heptane; cyclohexane; and methylcyclohexane.
  • Alicyclic hydrocarbon solvents such as dichloromethane, dichloroethane, chloroform, dibromoethane, etc., aromatic hydrocarbon solvents such as benzene, cyclobenzene, toluene, xylene, etc., dimethyl ether, Ether solvents such as diisopropyl ether, tetrahydrofuran, dimethoxetane, 1,3-dioxolan and 1,4-dioxane; nitrile solvents such as acetonitrile and propionitrile; Examples include amide solvents such as methylformamide and dimethylacetamide.
  • solvents may be used alone or as a mixed solvent of two or more.
  • these solvents more preferred are halogenated hydrocarbon solvents, aromatic hydrocarbon solvents, ether solvents, etc.
  • halogenated hydrocarbon solvents e.g., dichloromethane, toluene, xylene, tetrahydrofuran, etc. It is more preferable because of its high selectivity and high reaction selectivity and yield.
  • the amount of these solvents to be used is not particularly limited, but is usually about 1 to 50 times, preferably about 5 to 20 times the volume of the compound represented by the general formula [2]. .
  • the reaction temperature is usually about ⁇ 70 to 100 ° C., preferably about 170 to 0 ° C., and is maintained for about 5 minutes to 5 hours, preferably about 5 minutes to 5 hours.
  • the reaction can be carried out smoothly by reacting for about 10 minutes to 3 hours.
  • the amount of the diazo compound represented by the general formula [3 ⁇ ] relative to the compound represented by the general formula [2] is preferably about 0.5 to 5 moles per 1 mol of the former. Is used in a range of about 0.7 to 4 times mol.
  • the amount of the metal compound represented by the general formula [4] to the compound represented by the general formula [2] is about 0.5 to 2.5 times as much as 1 mol of the former. Degree, preferably in the range of about 0.7 to 2 times mol.
  • the amount of the base used relative to the compound represented by the general formula [2] is about 1 to 8 moles, preferably about 1.4 to 4 moles per mole of the former. A range is adopted.
  • the generated ⁇ depends on the kind of the diazo compound represented by the general formula [3] and the metal compound represented by the general formula [4] and various reaction conditions. Although the ratio of —body and / 3-body is slightly different, the target content of 3-body is usually about 85% or more.
  • a desired azetidinone compound can be obtained by a post-treatment method known per se, that is, for example, by solvent extraction, phase transfer, crystallization, recrystallization, various chromatographies, or the like. .
  • Toxic-3-[(R) -1-tert-butyldimethylsilyloxetyl] -azetidine-2-one 577.4 mg (2.0 mmo 1) of methylene chloride solution (5 mL) was added dropwise. Then, the mixture was further stirred at ⁇ 40 ° C. for 1 hour. The reaction mixture was poured into a 10% aqueous sodium hydrogen carbonate solution to stop the reaction, and the organic layer was separated and washed with water. As a result of analysis by high performance liquid chromatography, it was found that 3: ⁇ 95: 5.
  • Example 1 various metal compounds shown in Table 1 below were used in place of titanium tetrachloride, and the reaction and post-treatment were performed in the same manner as in Example 1 except for the above.
  • the same azetidinone compounds were obtained in the following yields and production ratios, respectively. The results are summarized in Table 1.
  • Table 1 Table 1
  • Example 6
  • Example 2 various reaction solvents shown in Table 2 below were used in place of methylene chloride. Other than that, the reaction and post-treatment were performed in the same manner as in Example 1, and the same as in Example 1 / 01615 The azetidinone compounds were obtained in the following yields and production ratios, respectively. The results are summarized in Table 2. '' Table 2
  • the present invention relates to an azetidinone compound which is an important synthetic intermediate for industrially producing a 1 / 3-methylcarbapanem derivative which is suitably used for producing a potent antibacterial substance useful as an antibacterial substance. It has a remarkable effect in that it provides a method for selective production under mild conditions in a short process with high yield.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

L'invention concerne un procédé permettant d'obtenir sélectivement un produit intermédiaire pendant la synthèse d'un agent antibactérien de type carbapenem comportant un groupe méthyle en position 1'-β. Le procédé de l'invention permet d'obtenir ce produit en peu de temps, avec un rendement élevé et dans des conditions douces, et de supprimer les problèmes apparaissant dans le procédé actuel. Plus particulièrement, l'invention concerne un procédé destiné à produire un composé azétidinone présentant une configuration 1'-β, et consistant à réaliser une réaction représentée par la formule (I) en présence d'un composé métallique spécifique et d'une base. Dans cette formule, R1 représente hydrogène ou un groupe hydroxy-protecteur, L représente un groupe partant, R2 représente hydrogène ou alkyle inférieur, R3 représente alkyle, aralkyle, etc., et X représente oxygène ou soufre.
PCT/JP2003/001615 2002-03-25 2003-02-17 Procede de production de composes azetidinone WO2003080571A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
KR10-2004-7008611A KR20040095198A (ko) 2002-03-25 2003-02-17 아제티디논 화합물의 제조방법
AU2003211227A AU2003211227A1 (en) 2002-03-25 2003-02-17 Process for producing azetidinone compounds

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2002-82560 2002-03-25
JP2002082560A JP2003277390A (ja) 2002-03-25 2002-03-25 アゼチジノン化合物の製造方法

Publications (1)

Publication Number Publication Date
WO2003080571A1 true WO2003080571A1 (fr) 2003-10-02

Family

ID=28449147

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2003/001615 WO2003080571A1 (fr) 2002-03-25 2003-02-17 Procede de production de composes azetidinone

Country Status (5)

Country Link
JP (1) JP2003277390A (fr)
KR (1) KR20040095198A (fr)
CN (1) CN1277819C (fr)
AU (1) AU2003211227A1 (fr)
WO (1) WO2003080571A1 (fr)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010013223A1 (fr) 2008-07-30 2010-02-04 Ranbaxy Laboratories Limited Procédé de préparation de composés carbapénèmes
CN101891665B (zh) * 2009-05-22 2013-02-06 上海医药工业研究院 (3s,4s)-4-乙酰基-3-((r)-1-羟基乙基)-2-氮杂环丁酮及其制备方法
WO2011048583A1 (fr) 2009-10-23 2011-04-28 Ranbaxy Laboratories Limited Procédé pour la préparation de composés de carbapénème
CN102936217A (zh) * 2012-11-08 2013-02-20 浙江新东港药业股份有限公司 一种培南中间体的制备方法
CN103553995A (zh) * 2013-11-13 2014-02-05 凯莱英医药集团（天津）股份有限公司 一种制备培南类抗生素中间体的方法
WO2015070394A1 (fr) * 2013-11-13 2015-05-21 凯莱英医药集团（天津）股份有限公司 Procédé de préparation d'un intermédiaire d'antibiotiques pénem

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0195963A1 (fr) * 1985-03-19 1986-10-01 Bayer Ag Procédé de préparation d'intermédiaires de carbapénème
US4863916A (en) * 1986-05-26 1989-09-05 Bayer Aktiengesellschaft Substituted 6-hydroxymethyl-carbapenem antibiotics
EP0409331A2 (fr) * 1989-07-18 1991-01-23 Merck & Co. Inc. Procédé de préparation de 2-diazo-3-trisubstitués silyloxy-3-butènoates
WO1993010364A1 (fr) * 1991-11-22 1993-05-27 Paul Francis Harding Ensemble comprenant un systeme de fixation
JPH0881439A (ja) * 1994-07-14 1996-03-26 Nippon Soda Co Ltd アゼチジノン化合物及びその製造方法
WO1999052908A1 (fr) * 1998-04-16 1999-10-21 Merck & Co., Inc. Preparation de produits intermediaires des carbapenems catalysee au titane
JP2000007652A (ja) * 1998-06-23 2000-01-11 Nippon Soda Co Ltd アゼチジノン誘導体の製造方法

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0195963A1 (fr) * 1985-03-19 1986-10-01 Bayer Ag Procédé de préparation d'intermédiaires de carbapénème
US4863916A (en) * 1986-05-26 1989-09-05 Bayer Aktiengesellschaft Substituted 6-hydroxymethyl-carbapenem antibiotics
EP0409331A2 (fr) * 1989-07-18 1991-01-23 Merck & Co. Inc. Procédé de préparation de 2-diazo-3-trisubstitués silyloxy-3-butènoates
WO1993010364A1 (fr) * 1991-11-22 1993-05-27 Paul Francis Harding Ensemble comprenant un systeme de fixation
JPH0881439A (ja) * 1994-07-14 1996-03-26 Nippon Soda Co Ltd アゼチジノン化合物及びその製造方法
WO1999052908A1 (fr) * 1998-04-16 1999-10-21 Merck & Co., Inc. Preparation de produits intermediaires des carbapenems catalysee au titane
JP2000007652A (ja) * 1998-06-23 2000-01-11 Nippon Soda Co Ltd アゼチジノン誘導体の製造方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
REIDER P.J. ET AL., TETRAHEDRON LETTERS, vol. 23, no. 22, 1982, pages 2293 - 2296, XP002969931 *

Also Published As

Publication number Publication date
JP2003277390A (ja) 2003-10-02
CN1610663A (zh) 2005-04-27
KR20040095198A (ko) 2004-11-12
AU2003211227A1 (en) 2003-10-08
CN1277819C (zh) 2006-10-04

Similar Documents

Publication Publication Date Title
JPH0557980B2 (fr)
WO2003080571A1 (fr) Procede de production de composes azetidinone
HU192819B (en) Process for preparing antibacterial penemic derivatives
EP0632037B1 (fr) Procédé pour la préparation des dérivés 4-substituées d'azetidinone
US4675396A (en) 7-Oxo-4-thia-1-azabicyclo(3,2,0)heptane derivatives
KR100886347B1 (ko) 키랄 보조제를 이용한 4-비엠에이의 입체선택적 제조방법
JPH075590B2 (ja) ４−置換β−ラクタム化合物
WO2004043961A1 (fr) Procede de production d'un compose de carbapenem pour l'administration par voie orale
JPWO2004043973A1 (ja) 経口投与用カルバペネム化合物の新規合成中間体及びその製造方法
WO2004035539A1 (fr) Procede destine a la fabrication de carbapenem et intermediaire utilise dans sa fabrication
JP3388874B2 (ja) β−ラクタム化合物の製造方法
JP4213229B2 (ja) アゼチジノン誘導体の製造方法
JPH0782249A (ja) ４−置換アゼチジノン誘導体の製造法
JPH06256327A (ja) ４−置換アゼチジノン誘導体の製造方法
JP4294124B2 (ja) アゼチジノン誘導体の製造方法
KR930007261B1 (ko) 7β-아미노-3-[3-(4-치환된 테트라졸린-5-티온-1-일)프로펜-1-일]-3-세펨-4-카르복실산 유도체 및 그 제조방법
JP2512550B2 (ja) ２―メチル―１―オキサデチアセフアロスポリン合成用中間体及びその製造法
KR100283608B1 (ko) 1-베타메틸-2-포르밀카바페넴유도체의제조방법
US5399679A (en) (1'R,3S,4R)4-acylthio azetidinones
US5145957A (en) Stereoselective synthesis of a chiral cis 3-beta hydrogen (3R) 4-aroyloxy azetidinone
JPH0782248A (ja) ４−置換アゼチジノン誘導体の製造方法
JPH0713058B2 (ja) ４―置換アゼチジノン誘導体の製造方法
JPH05500210A (ja) ペネムの製造方法
JPH05239020A (ja) ３−［（ｒ）−１−（置換オキシカルボニルオキシ）エチル−４−置換−２−アゼチジノンの製造法
JPS6332351B2 (fr)

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SC SD SE SG SK SL TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 1020047008611

Country of ref document: KR

WWE Wipo information: entry into national phase

Ref document number: 2003801808X

Country of ref document: CN

WWE Wipo information: entry into national phase

Ref document number: 2394/CHENP/2004

Country of ref document: IN

122 Ep: pct application non-entry in european phase