4-[4-[(5S)-5-(Aminomethyl)-2-oxo-3-oxazolidinyl]phenyl]-3-morpholinone Hydrochloride

12.The intermediate 4-(4-aminophenyl)-3-morpholinone (1) of the anticoagulant rivaroxaban was prepared by two methods: ①Bromobenzene was successively reacted with ethanolamine and chloroacetyl chloride to obtain 4-benzene The morpholinone is then nitrated to reduce to 1, and the total yield is about 32%; ②Bromobenzene is first nitrated, and then reacted with ethanolamine to obtain 2-(4-nitroanilino)ethanol, which is then closed by chloroacetyl chloride. The reduction reaction produces 1, and the total yield is about 47%.

Rivaroxaban is a new type of anticoagulant that can be directly taken orally. It directly inhibits the activation of coagulation factor Xa, has a definite anticoagulant effect, does not require continuous monitoring, and has high safety. With the clinical application of rivaroxaban , The demand for rivaroxaban will gradually increase. The chemical name of rivaroxaban is 5-chloro-N-(((5S) -2-oxo-3-[4- (3-oxo- 4-morpholinyl)phenyl)-1,3-oxazolidine-5-yl)methyl-2-thiophenecarboxamide. There are currently two synthetic routes reported in the literature, and both routes are used An intermediate 4-(4-aminophenyl)-3-morpholinone. Although there are reports on the synthesis of 4-(4-aminophenyl)-3-morpholinone at home and abroad, there is a relatively high price of reaction raw materials. High, difficult to buy, or the reaction operation requirements are too high, difficult to grasp, not conducive to environmental protection and other deficiencies, and do not meet the requirements of industrialized mass production. Optimize the key intermediate of rivaroxaban 4-(4-aminophenyl)- The production process of 3-morpholinone and the reduction of the price of raw materials will definitely promote the promotion and application of rivaroxaban. There is no report on the synthesis of rivaroxaban in China. We are at rivaroxaban The key intermediate 4-(4-aminophenyl)-3-morpholinone synthetic route and technology have been innovatively studied. Two bromobenzene and p-nitrobromobenzene as starting materials are proposed. Process route. Focus on the cyclization process of 3-morpholinone ring.