磷酸特地唑胺的合成新方法

A New Synthetic Route Toward Tedizolid Phosphate

以(5R)-3-(4-溴-3-氟苯基)-5-羟甲基噁唑烷-2-酮为起始原料,在[Pd Cl2(dppf)]·CH2Cl2催化下与联硼酸频那醇酯反应得到硼化物,继而与5-溴-2-(2-甲基-2H-四唑-5-基)吡啶进行Suzuki反应得到特地唑胺,收率82.9%。分别考察了催化体系对硼化反应和Suzuki反应的影响,确定了较佳的反应条件。特地唑胺与二苄基N,N-二异丙基亚磷酰胺反应得到二苄基保护的磷酸特地唑胺,随后经Pd/C脱苄得到磷酸特地唑胺,总收率66.2%。

Tedizolid with a yield of 82. 9% was synthesized by the Suzuki coupling reaction of 5-bromo-2-（ 2-methyl-2H-tetrazol-5-yl） pyridine and（ 5R）-3-（ 4-bromo-3-fluorophenyl）-5-（ hydroxymethyl）-2-oxazolidinone which was prepared from bis（ pinacolato） diboron using 1,1＇-bis（ diphenylphosphino） ferrocene-palladium（ Ⅱ）dichloride dichloromethane complex as the catalyst. The effect of the catalytic system on the reaction of the borylation reaction and Suzuki reaction was investigated respectively,and the optimum reaction conditions were determined. Tedizolid phosphate was obtained by reaction of tedizolid with dibenzyl N, Ndiisopropylphosphoramidite,and subsequent debenzylation with Pd / C. The total yield is 66. 2%.