The Study On The Process Of(S)-1-amino-2-(1'-methoxy-1'-ethyl)Propylpyrrolidine

(S)-1-amino-2-(1'-methoxy-1'-ethyl)propylpyrrolidine is a widely used organic intermediates.But its synthesis methods exist many disadvantages including:raw materials are expensive, reaction conditions are rigour,processing is complex,yield is low, cause environmental pollution, solvent is not easy to recycle.We employed L-proline to form L-proline ethyl ester,using thionyl chloride as the catalyst,and then used benzyl chloride and sodium hydroxide to protect the N atom,dry THF as the solvent undergo Grignard reaction,dimethyl sulfate and sodium hydroxide as the methylate reagent,under the catalytic hydrogenation of palladium/carbon(10%) to strip the benzyl group,mildly synthesis N-nitro compound under the condition of sodium and acetic acid,and finally reducted by zinc and acetic acid to form the end product.The major content and conclusion are:1.To synthesis L-proline ethyl ester,we invested the influence of using hydrochloric acid and thionyl chloride as catalyst on the productivity,and be certen that even the amout of thionyl chloride is far more less than hydrochloric acid,the productivity is higher.So,we make sure that use thionyl chloride as the catalyst,and the mole ratio with the L-prolin is1.4:1,and the best reaction condition is55℃and6h.2. To synthesis (S)-1-benzyl-2-carboxyethyl-pyrrolidine, we invested the influence of the dosage of benzyl chloride, base and temperature on the productivity.The result showed that the best reaction condition are the mole ratio of benzyl chloride and L-proline ethyl ester is1.4:1,equivalent sodium hydroxide,65℃.3. To synthesis (S)-1-benzyl-2-(1'-hydroxy-1'-ethyl)propyl-pyrrolidine, we invested the influence of the dosage of bromoethane ong the productivity. The result showed that the best reaction condition are the mole ratio of bromoethane and (S)-1-benzyl-2-carboxyethyl-pyrrolidine is2.4:1.4. To synthesis (S)-1-benzyl-2-(1'-methoxy-1'-ethyl)propyl-pyrrolidine, we invested the influence of the dosage of dimethyl sulfate,base and tempreture on the productivity. The result showed that the best reaction condition are the mole ratio of dimethyl sulfate and (S)-1-benzyl-2-(1'-hydroxy-1'-ethyl)propyl-pyrrolidine is1.2:1, sodium hydroxide is two equivalent of dimethyl sulfate,65℃5. To synthesis (S)-2-(1'-methoxy-1'-ethyl)propyl-pyrrolidine, we invested the influence of the dosage of palladium/carbon,and the pressure of hydrogen. The result showed that the best reaction condition are palladium/carbon:(S)-1-benzyl-2-(1'-methoxy-1'-ethyl)propyl-pyrrolidine is0.07(W/W),the pressure is0.7Mpa.6. To synthesis (S)-N-nitro-2-(1'-methoxy-1'-ethyl)propyl-pyrrolidine, we invested the influence of the dosage of sodium nitrile and solvent on the productivity. The result showed that the best reaction condition are the mole ratio of sodium nitrile and (S)-2-(1'-methoxy-1'-ethyl)propyl-pyrrolidine is1.5:1,THF:H2O=1:1(V/V).7.To synthesis (S)-1-amino-2-(1'-methoxy-1'-ethyl)propylpyrrolidine, we invested the influence of reducing agent and tempreture on the productivity. The result showed that the best reaction condition are the mole ratio of Zinc and (S)-N-nitro-2-(1-methoxy-2-ethyl)propyl-pyrrolidine is4:1,65℃.Our work give the synthesis process of (S)-1-amino-2-(1'-methoxy1'-ethyl)propylpyrrolidine.and this route is less pollution,easy operation, simple post-treatment.and low cost.