L-α-(3,4-二甲氧基苄基)-α-脲基丙酸的合成新工艺

A Novel Access to Synthesize L-α-(3,4-Dimethoxybenzyl)-α-ureidopropanoic Acid

研究了卡比多巴中间体L-α-(3,4-二甲氧基苄基)-α-脲基丙酸(1)的合成新工艺。以L-α-(3,4-二甲氧基苄基)-α-氨基丙酸盐酸盐(2)为起始原料,首先在甲醇中氯化氢气体催化下进行氨基酸的酯化反应,得到L-α-(3,4-二甲氧基苄基)-α-氨基丙酸甲酯(3),收率90.7%;然后在三乙胺存在下,用双(三氯甲基)碳酸酯(BTC)法对氨基进行氯甲酰化、用氨气进行氨解,得到L-α-(3,4-二甲氧基苄基)-α-脲基丙酸甲酯(4),收率77.7%;最后用浓盐酸水解得到目标产物(1),收率91.5%,三步总收率达64.5%。重点考察了氯化氢气体、BTC及盐酸用量对反应收率的影响。采用核磁共振氢谱和碳谱,质谱对有关化合物进行了结构表征。该工艺条件温和,操作简便,环境友好,收率良好,具有潜在的工业应用前景。

A novel access to synthesize L-α-（3,4-dimethoxybenzyl）-α-ureidopropanoic acid （1） was described. The title compound was synthesized from L-α-（3,4-dimethoxybenzyl）-α-aminopropanoic acid hydrochloride 2 with a total yield of 64.5%. The esterification of compound 2 was carried out in methanol by using hydrochloride gas as catalyst to afford methyl L-α-（3,4-dimethoxybenzyl）-α-aminiopropanoate 3 with 90.7% yield; then the chloroformylation and ammonolysis of the product 3 were conduct respectively by using bis（trichloromethyl）carbonate （BTC） in the presence of triethylamine and NH3 in dichloromethane separately to give methyl L-α-（3,4-dimcthoxybenzyl）-α-ureidopropanoate 4 with 77.7% yield. Hydrolysis of compound 4 in concentrated hydrochloric acid could get the title compound 1 with the yield of 91.5%. The effects of the amounts of hydrochloride gas, BTC and concentrated hydrochloric acid on product yields were investigated. The synthetic compounds were characterized by ^1H-NMR, ^13C-NMR and mass spectra, respectively. The advantages of the present procedure are simple operation, mild reaction condition, friendly environment and high yield, therefore it can be considered of having good prospect for industrial application.