“一锅法”合成14-O-[(2-氨基-1, 1-二甲基乙基)硫甲羰基]目特林

A One-pot Method for the Synthesis of 14-O-[(2-Amino-1, 1-dimethylethyl)thiomethylcarbonyl]mutilin

摘要:

以截短侧耳素、对甲苯磺酰氯和二甲基半胱胺盐酸盐为主要原料，以乙醚为溶剂，采用一锅法合成沃尼妙林中间体14-O-[(2-氨基-1, 1-二甲基乙基)硫甲羰基]目特林。最佳工艺条件：n(截短侧耳素): n(对甲苯磺酰氯): n(二甲基半胱胺盐酸盐)=1:1.1:1.1；相转移催化剂为四丁基溴化铵，用量为1.6 g；反应温度为30 ℃；反应时间为2.5 h；目标产物收率达91 %。并用正交设计法对主要工艺条件进行了优化，结果与单因素实验结果相同。产品结构通过核磁共振波谱，红外光谱进行了表征，测定了产物的熔点。

Abstract:

Valnemulin intermediate, 14-O-[(2-Amino-1, 1-dimethylethyl)thiomethylcarbonyl]mutilin, was prepared by one-pot method with Pleuromutilin, 4-toluenesulfonyl chloride and dimethylcysteamine hydrochloride in diethyl ether. The optimum condition was given following: n(Pleuromutilin): n(4-toluene sulfonyl chloride): n(dimethyl cysteamine hydrochloride)= 1:1.1:1.1, tetrabutyl ammonium bromide was used as phase transfer catalyst, amount of tetrabutyl ammonium bromide was 1.6 g, and reaction time for 2.5 h, reaction temperature for 30 ℃, the yield of product was 91%. Orthogonal design of 4 factors at 3 levels was applied for main process conditions，results agreed with the single factor experimental data. The structure of target compound was characterized by 1HNMR, IR and melting point.