QF-1004B
Chemical Name: 6-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)piperidin-1-ylmethyl]-6,7-dihydrobenzofuran-4(5H)-one
项目整合开发状态: Preclinical
项目研究机构: Universidad de Santiago de Compostela (Originator), Universit?degli Studi di Pisa (Originator)
合成路线:Acidic hydrolysis of the enol ether groups of 1,4-dihydro-3,5-dimethoxybenzyl alcohol (I) gave diketone (II).Subsequent condensation of (II) with chloroacetaldehyde in the presence of NaHCO3,followed by dehydration of the intermediate (III) upon acidic treatment,yielded the tetrahydrobenzofuranone (IV).Tosylate (V) was then prepared by reaction of alcohol (IV) with p-toluenesulfonyl chloride in cold pyridine.Finally,nucleophilic displacement of the tosylate group with benzisoxazolylpiperidine (VI) in N-methylpyrrolidone provided the title amine.
📌 参考资料/链接：
参考文献标题:Conformationally constrained butyrophenones with affinity for dopamine (D1,D2,D4) and serotonin (5-HT2A,5-HT2C) receptors: Synthesis of aminomethylbenzo[b]furanones and their evaluation as antipsychotics
文献作者:Ravi�? E.; Casariego,I.; Masaguer,C.F.; Fontenla,J.A.; Montenegro,G.Y.; Rivas,M.E.; Loza,M.I.; Enguix,M.J.; Villazon,M.; Cadavid,M.I.; Demontis,G.C.
参考来源:J Med Chem 2000,43(24),4678
📄 详细内容
合成路线:Acidic hydrolysis of the enol ether groups of 1,4-dihydro-3,5-dimethoxybenzyl alcohol (I) gave diketone (II).Subsequent condensation of (II) with chloroacetaldehyde in the presence of NaHCO3,followed by dehydration of the intermediate (III) upon acidic treatment,yielded the tetrahydrobenzofuranone (IV).Tosylate (V) was then prepared by reaction of alcohol (IV) with p-toluenesulfonyl chloride in cold pyridine.Finally,nucleophilic displacement of the tosylate group with benzisoxazolylpiperidine (VI) in N-methylpyrrolidone provided the title amine.
参考文献标题:New CNS agent precursors.A simple and efficient route for synthesis of 6-aminomethyl-4,5,6,7-tetrahydrobenzofuran-4-ones as conformationally constrained butyrophenone analogues
文献作者:Casariego,I.; et al.
参考来源:Tetrahedron Lett 1997,38(31),5555