2-AMINO-5-METHYL-THIOPHENE-3-CARBOXYLIC ACID METHYL ESTER synthesis

Yield: 73.6%

Reaction Conditions:

with morpholine;sulfur in N,N-dimethyl-formamide at 50;

Steps:

27.a a) 2-amino-5-methylthiophene-3-carboxylic acid methyl ester (27a)
The sulfur powder (960.0mg, 30.0mmol)In a single mouth bottle,Add DMF 5 mL,Were successively added methyl cyanoacetate (3.39g, 30.0mmol),Morpholine (1.48 g, 17.0 mmol),The reaction solution was dark brown,Propionaldehyde (1.74 g, 30.0 mmol) was added,50 ° C overnight.After completion of the reaction, the mixture was cooled to room temperature,Add appropriate amount of water,Ethyl acetate was extracted three times,The combined organic phases were washed with saturated brine,Dried over anhydrous magnesium sulfate,The crude product was distilled under reduced pressure.Separation and purification by column chromatography,To give a pale yellow solid.Yield: 73.6%

References:

Zhejiang University;Shanghai Institute of Materia Medica, Chinese Academy of Sciences;Chen, Jianzhong;Xie, Xin;Qian, Haiyan;Chen, Lili;Wang, Zhilong CN106167497, 2016, A Location in patent:Paragraph 0241; 0242; 0243