S-(-)-2-羧基吲哚啉的制备研究

Study on the Synthesis of S-(-)-2-Carboxyindoline

S-(-)-2-羧基吲哚啉是合成培多普利的关键中间体。以邻硝基甲苯为原料,经缩合、硝基还原、杂环还原、水解制得2-羧基吲哚啉外消旋体,总收率40.6%。其中,杂环还原采用了Pd-C催化加氢,在160℃、6.2MPa条件下,收率达89.1%,且催化剂可以回收利用,较金属-酸还原体系对环境更友好,成本更低。采用了新的拆分试剂L-肉碱草酸盐,经酰化、酯化、部分结晶、水解得到S-(-)-2-羧基吲哚啉,收率32.0%,??α52809=?27.5??(c=1.0,DMSO)。该制备工艺具有较好的应用价值。

A general synthetic mute of S-（-）-2-Carboxyindoline was proposed which started from o-nitrotoluene and diethyl oxalate, via condensation, nitro-group reduction, heterocyclic reduction and hydrolysis, 2-carboxyindoline was achieved with total yield of 40.6%. Especially, using 10% Pd-C as catalysts, the heterocycle is reduced easily with hydrogen at 160℃ and 6.2 MPa, the catalysts also can be reclaimed. Through steps of chlorination, esterification, fractional crystallization, and hydrolysis, the S-（-）-2-carboxyindoline was resoluted with L-carnitine oxalate as the chiral resolution reagent. The titled product can be achieved with 32% yield and [a^20 589 = -27.5] （c =1.0, DMSO）.