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    • 6. 发明授权
    • Process for preparing 4-substituted azetidinone derivatives
    • 制备4-取代的氮杂环丁酮衍生物的方法
    • US5731431A
    • 1998-03-24
    • US664969
    • 1996-06-10
    • Yuuki NakagawaKiyohito ImaiTamio Hara
    • Yuuki NakagawaKiyohito ImaiTamio Hara
    • C07D205/08C07D403/06C07D413/06C07D417/06
    • C07D205/08Y02P20/55
    • A process for preparing 4-substituted azetidinone derivatives of the formula: ##STR1## wherein R is hydrogen or an easily removable protecting group; R.sup.1 is alkyl which can be substituted by hydroxy which can be protected or halogen; R.sup.2 is hydrogen or alkyl; R.sup.3 is alkyl, trialkylsilyl, phenyl which can be substituted by alkyl, alkoxy, nitro or halogen, cycloalkyl, naphthyl, anthracenyl, fluorenyl, benzothiazolyl or naphthalimidyl; and R.sup.4 is an electron withdrawing group or can form a ring together with R.sup.3, which comprises reacting an azetidinone derivative of the formula: ##STR2## wherein R and R.sup.1 are as defined above, and Z is a leaving group, and an imide compound of the formula: ##STR3## wherein R.sup.2, R.sup.3 and R.sup.4 are as defined above, in the presence of a titanium compound of the formula: Ti(Cl).sub.n (OR.sup.5).sub.m wherein R.sup.5 is lower alkyl, n and m are respectively an integer from 0 to 4, provided that n plus m always makes 4, and a base. The process of the present invention is an industrially advantageous process using a titinium compound which is inexpensive and easy to handle. 4-Substituted azetidinone compounds prepared according to the process of the present invention can be easily hydrolyzed to a carboxylic acid which is an important intermediate for the synthesis of carbapenem compounds.
    • 制备下式的4-取代的氮杂环丁酮衍生物的方法:其中R是氢或易于除去的保护基; R1是可以被可被保护的羟基或卤素取代的烷基; R2是氢或烷基; R3是烷基,三烷基甲硅烷基,可被烷基,烷氧基,硝基或卤素取代的苯基,环烷基,萘基,蒽基,芴基,苯并噻唑基或萘基亚氨基; 并且R4是吸电子基团或可以与R3一起形成环,其包括使下式的氮杂环丁酮衍生物:其中R和R 1如上定义,Z是离去基团的酰亚胺化合物 在下式的钛化合物存在下,其中R 2,R 3和R 4如上所定义的式:其中R 5为低级烷基,n和m分别为 0到4,只要n加m总是4,和一个基数。 本发明的方法是使用廉价且易于处理的钛化合物的工业上有利的方法。 4-取代的根据本发明方法制备的氮杂环丁酮化合物可以容易地水解成羧酸,羧酸是合成碳青霉烯化合物的重要中间体。
    • 8. 发明授权
    • Process for the production of 4-substituted azetidinone derivative
    • 用于制备4-取代的氮杂环丁酮衍生物的方法
    • US5792861A
    • 1998-08-11
    • US743327
    • 1996-11-04
    • Tamio HaraYuuki NakagawaNobuo MatsuiShigemi Suga
    • Tamio HaraYuuki NakagawaNobuo MatsuiShigemi Suga
    • C07D413/06C07F7/18C07D205/08C07D403/06C07D417/06
    • C07D413/06C07F7/1892Y02P20/55
    • The present invention provides a process for the production of a 4-substituted azetidinone. The process comprises reacting ##STR1## wherein R represents a hydrogen atom or a protecting group for N, R.sup.1 represents an alkyl which may be a substituent having an unprotected or protected hydroxyl group; and Z represents a leaving group; with ##STR2## wherein R.sup.2 represents hydrogen or alkyl, R.sup.3 and R.sup.4 each represent hydrogen, alkyl, alkenyl, alkynyl, phenyl, cycloalkyl, or naphthyl, or R.sup.3 and R.sup.4, together with the carbon atom to which they are bonded, form a ring system; X and Y each represent oxygen, sulfur or N-r.sup.1, wherein r.sup.1 represents a hydrogen atom or lower alkyl; A, B, D and E each represent nitrogen or C-r.sup.2, wherein r.sup.2 represents hydrogen, halogen, lower alkyl or lower alkoxy, provided that at least two of A, B, D and E are C-r.sup.2 ; and a ring involving G, J and K has two carbon/carbon double bonds therein and one of G, J and K represents oxygen, sulfur or N-r.sup.1 while the remaining two represent C-r.sup.2 ; in the presence of M(Hal).sub.n (R.sup.5).sub.m (V) wherein M represents a metal atom; Hal represents halogen; R.sup.5 represents lower alkyl, lower alkoxy, phenoxy, substituted phenoxy or cyclopentadienyl; and n and m are each 0, 1, 2, 3, 4 or 5, provided that n+m stands for the valence of M; and a base to thereby give: ##STR3##
    • 本发明提供了制备4-取代的氮杂环丁酮的方法。 该方法包括使其中R表示氢原子或N为保护基的化合物(III)反应,R 1表示可以是具有未被保护或被保护的羟基的取代基的烷基; Z表示离去基团; 代表氢或烷基,R3和R4各自表示氢,烷基,烯基,炔基,苯基,环烷基或萘基,或R3和R4与它们所键合的碳原子一起形成环系; X和Y各自表示氧,硫或N-r1,其中r1表示氢原子或低级烷基; A,B,D和E各自表示氮或C-R 2,其中R 2表示氢,卤素,低级烷基或低级烷氧基,条件是A,B,D和E中的至少两个为C-R 2; 涉及G,J和K的环在其中具有两个碳/碳双键,G,J和K之一表示氧,硫或N-r1,其余两个表示C-r2; 在M(Hal)n(R5)m(V)的存在下,其中M表示金属原子; 卤代表卤素; R5表示低级烷基,低级烷氧基,苯氧基,取代的苯氧基或环戊二烯基; n和m分别为0,1,2,3,4或5,条件是n + m代表M的化合价; (II-1)或(II-2)所示的基础,从而得到: