Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1994-03-22
1997-08-12
Shah, Mukund J.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
540222, 540225, C07D50116
Patent
active
056567545
DESCRIPTION:
BRIEF SUMMARY
This is a national phase application filed under 37 C.F.R. 371 of PCT/JP93/01041 filed Jul. 26, 1993.
TECHNICAL FIELD
The present invention relates to a process for preparing cephem compounds having a broad antibacterial spectrum.
BACKGROUND ART
The Witting reaction is already known as a process for preparing 3-alkenyl cephem compounds (e.g., JP-A-120288/1991, JP-A-307885/1988, etc.).
Also known as a process for preparing 3-alkenyl, 3-aryl and 3-heterocyclic cephem compounds is the process wherein a cephem compound having an elimination group L (such as fluorosulfonyloxy group or trifluoromethylsulfonyloxy group) at the C(3)- position is reacted with an organotin compound in the presence of a palladium catalyst (JP-A-220195/1991 and JP-A-313483/1989).
These processes each use a compound having a cephem skeleton as the starting material and have problems, for example, in respect of the economy of the material or the number of steps involved in preparing the material.
Further a report was recently made on a process for preparing 3-alkenyl or 3-aryl cephem compounds, i.e., a process wherein an allenyl-.beta.-lactam compound found by us (Torii et al., Synlett, 1991, 888), represented by the general formula (1) and serving as the starting material is reacted with an organocopper reagent prepared in advance from an organotin compound and dimethyl cuprate, or an organolithium compound and cuprous iodide, or a Grignard reagent and cuprous iodide [Kant et al., Tetrahedron Letters, 33 (25), 3563 (1992)]. This process affords the desired cephem compound from an inexpensive penicillin compound by a short reaction step. With this process, however, the reaction must be conducted at an extremely low temperature (-100.degree. to -78.degree. C. ) which is industrially infeasible, further produces an undesirable 2-cephem compound as a by-product and encounters difficulty in purifying the desired product.
An object of the present invention is to provide a novel process for preparing various cephem compounds having a broad antibacterial spectrum from an allenyl-.beta.-lactam compound easily by a simplified reaction procedure under reaction conditions which can be industrially realized with ease, the lactam compound being readily available from an inexpensive penicillin compound by a short reaction step.
The present invention provides a process for preparing a cephem compound represented by the general formula (3) characterized in that an allenyl-.beta.-lactam compound represented by the general formula (1) is reacted with an organotin compound represented by the general formula (2) in the presence of a monovalent copper salt ##STR3## wherein R.sup.1 is a hydrogen atom, halogen atom, amino or protected amino, R.sup.2 is a hydrogen atom, halogen atom, lower alkoxyl, lower acyl, lower alkyl, lower alkyl having hydroxyl or protected hydroxyl as a substituent, hydroxyl or protected hydroxyl, or R.sup.1 and R.sup.2 form=0 when taken together, R.sup.3 is a hydrogen atom or carboxylic acid protecting group, R.sup.4 is aryl, aryl having a substituent, nitrogen-containing aromatic heterocyclic group or nitrogen-containing aromatic heterocyclic group having a substituent, and m is 0 or 2, a substituent, nitrogen-containing aromatic heterocyclic group or nitrogen-containing aromatic heterocyclic group having a substituent, R.sup.6 is lower alkyl, and n is 1 or 2, ##STR4## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.5 are the same as defined above.
Examples of groups mentioned herein are as follows. The term "halogen atom" as used hereinafter means, for example, fluorine, chlorine, bromine or iodine atom unless otherwise specified. The term "lower alkyl" means a straight-chain or branched C.sub.1.about.4 alkyl group such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl. The term "aryl" means, for example, phenyl, naphthyl or the like.
Exemplary of the protected amino represented by R.sup.1 are phenoxyacetamido, p-methylphenoxyacetamido, p-methoxyphenoxyacetamido, p-chlorophenoxyacetamido, p-bromophen
REFERENCES:
patent: 4870168 (1989-09-01), Baker
patent: 5132419 (1992-07-01), Lanz
patent: 5266691 (1993-11-01), Farino et al.
patent: 5420269 (1995-05-01), Baker
Hideo Tanaka, Yutaka Kameyama et al., Synlett (12), 1991, pp. 888-890.
Joydeep Kant & Vittorio Farina, Tetrahedron Letters, vol. 33, No. 25, pp. 3563-3566, 1992.
Kameyama Yutaka
Sasaoka Michio
Shiroi Takashi
Tanaka Hideo
Torii Shigeru
Otsuka Kagaku Kabushiki Kaisha
Rao Deepak R.
Shah Mukund J.
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