DL-苏式-对甲砜基苯丝氨酸乙酯的合成及拆分

Synthesis and Chiral Separation of DL-thero-p-methylsulfonylphenylserine Ethyl Ester

以对甲砜基苯丝氨酸铜为原料,浓硫酸为催化剂,考察了DL-苏式-对甲砜基苯丝氨酸乙酯的制备工艺。最佳的工艺条件为:n(对甲砜基苯丝氨酸铜)∶n(浓硫酸)∶n(乙醇)=1∶6∶50,反应温度83℃,反应时间10 h,0℃下析晶,氨析时的pH=7.5,在该条件下,DL-苏式-对甲砜基苯丝氨酸乙酯收率为92%。对酯化废液及氨析废液中的DL-苏式-对甲砜基苯丝氨酸乙酯进行回收,最终DL-苏式-对甲砜基苯丝氨酸乙酯的收率提高到98%左右。采用IR1、HNMR和HPLC对所合成的产物DL-苏式-对甲砜基苯丝氨酸乙酯进行了分析与表征。以D-酒石酸作为手性拆分剂,对DL-苏式-对甲砜基苯丝氨酸乙酯进行拆分,结果表明,拆分最佳工艺为:n(DL-苏式-对甲砜基苯丝氨酸乙酯)∶n(D-酒石酸)∶n(甲醇)=1∶1∶50,氨析过程中的pH=7.5时,D-苏式-对甲砜基苯丝氨酸乙酯收率为93%。

The preparation process of DL-thero-p-methylsulfonylphenylserine ethyl ester,using p-methylsulfonylphenylserine copper as raw material and concentrated sulfuric acid as catalyst,was studied in this paper.A study on the factors that influenced the preparation process reveals that the optimal conditions were as follows：n（p-methylsulfonylphenylserine copper）∶ n（concentrated sulfuric acid） ∶ n（ethanol）=1∶ 6∶ 50,the reaction temperature was 83 ℃,the reaction time was 10 h,the crystallization temperature was 0 ℃ and the value of pH,during the process of DL-thero-p-methylsulfonylphenylserine ethyl ester precipitating from ammonia,was 7.5.The yield of DL-thero-p-methylsulfonylphenylserine ethyl ester was approximately 92% under such optimal conditions.Then the DL-thero-p-methylsulfonylphenylserine ethyl ester was recycled from liquid waste which was produced during the esterification process and the process of DL-thero-p-methylsulfonylphenylserine ethyl ester precipitating from ammonia.After that,the yield of DL-thero-p-methylsulfonylphenylserine ethyl ester increased to approximately 98%.The products of the synthesis of DL-thero-p-methylsulfonylphenylserine ethyl ester were analysed and characterized by means of IR,1HNMR and HPLC.Chiral separation of DL-thero-p-methylsulfonylphenylserine ethyl ester was conducted,using D-tartaric acid as chiral selector.The results indicate that the yield of D-thero-p-methylsulfonylphenylserine ethyl ester was 93% under the optimal conditions as follows：n（DL-thero-p-methylsulfonylphenylserine ethyl ester）∶ n（D-tartaric acid）∶ n（methanol）=1∶ 1∶ 50,DL-thero-p-methylsulfonylphenylserine ethyl ester precipitated from ammonia when the value of pH was 7.5.