Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1996-11-06
2000-01-04
Berch, Mark L.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
540358, 540362, 540363, C07D20509, C07D205095, C07D205085, C07D20508
Patent
active
060111518
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The .beta.-lactam halide compounds (2) to be described below are important intermediates which can be readily made into derivatives such as 3-norcephem and isocephem (Can. J. Chem., 1978, 56, 1335).
BACKGROUND ART
The .beta.-lactam halide compound represented by the general formula (2) is prepared by reacting halogen molecules with an allenyl .beta.-lactam compound represented by the general formula (1) below as is already known (Can. J. Chem., 1978, 56, 1335). However, this process affords a mixture of .alpha., .beta.-lactam and .beta., .gamma.-position isomers depending on the kind of halogen molecule and is not usable in actuality. It is also reported that as shown in the diagram, a keto-form .beta.-lactam compound is enolized into an enol ether or vinyl halide, followed by halogenation with N-bromosuccinimide or N-chlorosuccinimide in the presence of a radical generating agent (JP-A-135859/1983). Since this process requires use of a hazardous reagent for reaction, processes which are industrially more feasible are desired ##STR3## wherein the group A, group S--D and group E are groups analogous respectively to the group R.sup.1 /R.sup.2, group R.sup.4 and group R.sup.3 of the invention to be described below.
An object of the present invention is to provide a process for preparing a .beta.-lactam halide compound represented by the general formula (2) through a simple procedure in a high yield with a high purity using an allenyl .beta.-lactam compound represented by the general formula (1) as the starting material, by developing a novel halogenating reagent having a high position selectivity.
DISCLOSURE OF THE INVENTION
The present invention provides a process for preparing a .beta.-lactam halide compound represented by the formula (2) characterized by halogenating the allenyl group of an allenyl .beta.-lactam compound represented by the formula (1) with a cupric halide and a metal halide to obtain the .beta.-lactam halide compound ##STR4## wherein R.sup.1 is a hydrogen atom or amino or protected amino, R.sup.2 is a hydrogen atom, halogen atom, lower alkoxyl, lower acyl, or lower alkyl having a hydroxyl group or protected hydroxyl group as a substituent, R.sup.3 is a hydrogen atom or carboxylic acid protecting group, and R.sup.4 is a hydrocarbon group which may have a substituent, or the group --S--S(O)n-Ar, n being 0 to 2, Ar being aryl which may have a substituent ##STR5## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are the same as defined above, X and Y are each halogen atom.
Examples of groups mentioned herein are as follows.
Exemplary of the protected amino represented by R.sup.1 are amido groups such as phenoxyacetamido, p-methylphenoxyacetamido, p-methoxyphenoxyacetamido, p-chlorophenoxyacetamido, p-bromophenoxyacetamido, phenylacetamido, p-methylphenylacetamido, p-methoxyphenylacetamido, p-chlorophenylacetamido, p-bromophenylacetamido, phenylmonochloroacetamido, phenyldichloroacetamido, phenylhydroxyacetamido, thienylacetamido, phenylacetoxyacetamido, .alpha.-oxophenylacetamido, benzamido, p-methylbenzamido, p-methoxybenzamido, p-chlorobenzamido, p-bromobenzamido, phenylglycylamido, phenylglycylamido having protected amino, p-hydroxyphenylglycylamido, p-hydroxyphenylglycylamido having protected amino and/or protected hydroxyl, etc.; imido groups such as phthalimido, nitrophthalimido, etc., in addition to the groups disclosed in Theodora W. Greene, 1981,"Protective Groups in Organic Synthesis" (hereinafter referred to merely as the "literature"), Chap. 7 (pp. 218.about.287). Examples of protective groups for the amino of phenylglycylamido group and p-hydroxyphenylglycylamido group are those disclosed in the literature, Chap. 7 (pp. 218.about.287). Examples of protective groups for the hydroxyl of p-hydroxyphenylglycylamido group are those disclosed in the literature, Chap. 2 (pp. 10.about.72).
Examples of halogen atom represented by R.sup.2 are fluorine, chlorine, bromine or iodine atom. Exemplary of the lower alkoxyl represented by R.sup.2 are straight-chain or branched C
REFERENCES:
patent: 5196530 (1993-03-01), Torii
patent: 5204458 (1993-04-01), Torri
TanakaBioorganic & Meidcinal Chemical Letters 3(11) 2253, 1993.
Baldwin, J. Chem Soc Chem Comm p. 81, Jan. 1987.
Kameyama Yutaka
Sasaoka Michio
Suzuki Daisuke
Tanaka Hideo
Torii Sigeru
Berch Mark L.
Otsuka Kagaku Kabushiki Kaisha
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