Method for synthesizing rivaroxaban intermediate, 4-(4-[(5S)-(aminomethyl)-2-oxo-1,3-oxazoligdin-3-YL]phenyl)morpholin-3-one

摘要

The present invention discloses novel methods for synthesizing Rivaroxaban intermediate, i.e., 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one. The novel methods provided in the present invention involve mild reaction conditions, convenient operations, easy purification, and low production costs, and thus the process is environmental-friendly and suitable for industrial production.

主权项

1. A method for synthesizing Rivaroxaban intermediate, 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one, selected from the following three methods:
method I, comprising:
step (1): the condensation of compound 1 with compound 2 to form compound 3; andstep (2): deprotecting compound 3 to provide compound 4, i.e., 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one, wherein the reaction scheme is described as follows: method II, comprising:
step (1): the condensation of compound 1 with compound 5 to form compound 3;step (2): deprotecting compound 3 to provide compound 4, i.e., 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one, wherein the reaction scheme is described as follows: and method III, comprising:
step (1): the condensation of compound 6 with compound 5 to form compound 7; andstep (2): hydrolyzing compound 7 to provide compound 4, i.e., 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one, wherein the reaction scheme is described as follows: