Facile Preparation of 4‑(4-Nitrophenyl)morpholin-3-one
via the Acid-Catalyzed Selective Oxidation of 4‑(4-Nitrophenyl)morpholine
by Sodium Chlorite as the Sole Oxidant
posted on 2020-09-25, 19:13authored byChaoyang Liu, Tao Yu, Tiannuo Yang, Haozhou Sun, Cheng Qin, Qiang Jia, Changhu Chu
4-(4-Nitrophenyl)morpholin-3-one
and 4-(4-aminophenyl) morpholin-3-one
are the key intermediates for rivaroxaban synthesis. A facile and
economically efficient process has been developed for the preparation
of these intermediates. Excellent yield of 4-(4-nitrophenyl)morpholine
is obtained by condensing 4-chloro nitrobenzene and morpholine, and
4-(4-nitrophenyl)morpholine is oxidized using inexpensive sodium chlorite
to achieve a good yield of the corresponding 4-(4-nitrophenyl)morpholin-3-one.
Finally, the key intermediate of rivaroxaban, 4-(4-aminophenyl) morpholin-3-one,
is achieved by the iron(III)-catalyzed reduction of the nitro group
with aqueous hydrazine. No high-cost materials were used, and the
process did not require column purification.