Method for synthesizing 4-thio-bicyclo [3.1.0]-2-hexene-6-formic ether

Abstract

The invention relates to the preparation of cyclopropane carboxylate, in particular to a method for synthesizing 4-thio-bicyclo [3.1.0]-2-hexene-6-formic ether under the mild condition of the catalysis of non-noble metal. The method comprises the following steps of: taking thiophene and ethyl diazoacetate as raw materials, adopting a compound of Cu or Co as a catalyst, adopting a compound which does not contain an alcoholic hydroxyl group, a carboxylic acid group, a primary amino radical and a secondary amino group as a solvent, dripping the ethyl diazoacetate or a solution thereof into the mixture of the catalyst and the thiophene, stirring, reacting for 5-24min at the temperature of 0-120 DEG C until a reaction mixture does not discharge gas any more, then distilling off the solvent andthe excessive thiophene and separating by the methods of column chromatography or reduced pressure distillation and the like to obtain the 4-thio-bicyclo[3.1.0]-2-hexene-6-formic ether, wherein calculated by molar weight, the use quantity of the thiophene in the reaction is 1-200 times that of the ethyl diazoacetate, the use quantity of the catalyst is 0.0001-100mol% of that of the ethyl diazoacetate, and the volume of the solvent is 0-50 times the volume of the thiophene. The invention has low cost, mild condition, better selectivity and higher economic value.

Description

technical field [0001] The invention relates to the preparation of cyclopropane carboxylate, in particular to a method for synthesizing 4-thiobicyclo[3.1.0]-2-hexene-6-carboxylate under non-noble metal-catalyzed mild conditions. Background technique [0002] Glutamate receptor modulators (agonists, antagonists) are closely related to human health. Mammalian cortical pyramidal cells use glutamate as an excitatory transmitter. The disorder and degeneration of nerve fibers in the cortex and cortical pyramidal cells of Alzheimer's patients lead to neuron damage, loss of function, and symptoms; while the conduction function is too strong, it will produce excitotoxicity, leading to neuron death , causing neurodegenerative diseases. Therefore, modulators of glutamate receptors have important effects in the treatment of neurological diseases. [0003] Monn, J.A.; Valli, M.J.; Massey, S.M.; et al. J. Med. Chem. 1999, 42(6), 1027-1040; Moher, E.D.; Monn, J.A.; Pedregal-Tercero, C. ...

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Problems solved by technology

In 1979, Porter adopted CuCl, CuP(OEt) 3 I, etc. catalyze the cyclopropanation reaction of butyl diazoacetate and thiophene, use pure diazoacetate to react, and the yield of cyclopropane compound is 10-20%; but use unpurified diazoacetate The reaction was carried out, and the yield decreased significantly

[0008] In 2005, Prez adopted TpxCu (Tpx) homoscorpionate ligand) to catalyze the cyclopropanation reaction of furan and diazoacetate, and the yield of the target product was about 30% (Caballero, A.; Daz-Requejo, M.M.; Trofimenko, S .; Belderrain, T.R.; Prez, P.J.J.Org.Chem., 2005, 70(15), 6101-6104); but there is no report on the reaction with thiophene as substrate

[0009] At present, there is no cheap and suitable method for large-scale synthesis of 4-thiobicyclo[3.1.0]-2-hexene-6-carboxylate

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