3-(2-chloro-1-oxopropyl)-spiro[2H-1,3-benzoxazine-2,1'-cyclohexan]-4(3H)-one and synthesis and application thereof

Abstract

The invention relates to the field of material synthesis, in particular to 3-(2-chloro-1-oxopropyl)-spiro[2H-1,3-benzoxazine-2,1'-cyclohexan]-4(3H)-one and synthesis and application thereof, aiming to solve the problem of restricted development of meropenem due to complicated existing methods for synthesizing 3-(2-Bromo-1-oxopropyl)-spiro[2H-1,3-benzoxazine-2,1'-cyclohexan]-4(3H)-one, strict reaction conditions and low yield. A method for preparing the 3-(2-chloro-1-oxopropyl)-spiro[2H-1,3-benzoxazine-2,1'-cyclohexan]-4(3H)-one includes steps of 1, placing intermediates I, pyridine, chloropropionyl chloride and reactive solvents into a reactor according to a molar ratio of 1:(1-3):(1-3):(5-10), carrying out reaction at the temperature of 30-50 DEG C under the control for 3-5 h, concentrating the solvents and cooling and crystallizing reaction products to obtain F-6; 2, adding mixed liquid of organic solvents and salt solution into the F-6 obtained in the step 1, completely dissolving the F-6, stirring the F-6 and the mixed liquid, allowing the F-6 and the mixed liquid to stand still and then layer, cooling separated organic phases obtained by means of layering, precipitating out solid, carrying out suction filtration on the solid and drying the solid to obtain refined products. Raw materials for synthesizing the F-6 are easily available, the method includes few reaction steps, reaction conditions are mild, only few byproducts are generated, the method is easy and convenient to implement, and the used solvents can be recycled.

Description

technical field [0001] The invention relates to the field of material synthesis, in particular to chloropropionyl spirobenzoxazine cyclohexane and its synthesis and application. Background technique [0002] Meropenem is another semi-synthetic carbapenem antibiotic for parenteral administration after imipenem-cilastatin was launched in the United States. Through its covalent bond and penicillin-binding proteins (PBPs) involved in cell wall synthesis, it inhibits the synthesis of bacterial cell walls, thereby playing an antibacterial role. It is sensitive to Gram-positive bacteria and Gram-negative bacteria, especially has strong antibacterial activity against Gram-negative bacteria. For example, the minimum inhibitory concentration (MIC) for about 90% of Enterobacter spp. is 0.08-0.15mg / L, more than 90% of Pseudomonas aeruginosa strains are highly sensitive to it (MIC<4mg / L), all Haemophilus Including ampicillin-resistant strains are highly sensitive to it (MIC 0.06-1mg...

AI Technical Summary

Problems solved by technology

[0007] The existing synthetic method of bromopropionylspirobenzoxazine cyclohexane is complicated to operate, the reaction conditions are harsh, and the yield is low cost. Harsh conditions and low yield restrict the development of meropenem. The present invention provides chloropropionyl spirobenzoxazine cyclohexane to replace bromopropionyl spirobenzoxazine cyclohexane as an intermediate in the synthesis of meropenem to overcome the existing bromine Disadvantages of propionylspirobenzoxazine cyclohexane as an intermediate

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