摘要
目的合成阿伐他汀的关键中间体 4 氟 α (2 甲基 1 氧丙基 ) γ 氧 N ,β 二苯基 苯丁酰胺 (1)。 方法以异丁酸、苯甲酰氯、Meldrum酸、苯胺等为原料 ,经氯化、缩合和胺解反应得到异丁酰乙酰苯胺 (4) ;以苯乙酸、氯化亚砜、氟苯、溴等为原料 ,经氯化、烃化和溴化反应得到 2 溴 1 (4 氟苯基 ) 苯乙酮 (7) ,化合物 4与 7经烃化反应得到目标产物 1。结果与结论合成路线原料易得 ,操作简便 ,收率较高 ,各主要化合物结构经质谱、核磁共振氢谱确证。
Aim To synthesize the key intermediate of atorvastatin 4-fluoro-α-(2-methyl-1-oxopropyl)-γ-oxo-N,β-diphenyl-benzenebutanamide.Method The target compound was synthesized by condensation of isobutyrylacetanilide(4)with 2-bromo-1-(4-fluorophenyl)-2-phenylethanone(7).Compound 4 was obtained from isobutyric acid by chlorination,condensation with Meldrum′s acid and ammonolysis,and compound 7 was synthesized from benzeneacetic acid by chlorination,acylation and bromination.Results and conclusion The starting materials in the synthetic route are easily available and the yield was reasonable.The structure of the main intermediate was verified by ESI-MS and 1H-NMR.
出处
《中国药物化学杂志》
CAS
CSCD
2005年第1期48-50,共3页
Chinese Journal of Medicinal Chemistry
