898543-06-1

Rivaroxaban intermediate.

Nonflammable

The general procedure for the synthesis of (S)-4-(4-(5-(aminomethyl)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-5-oxazolidinyl]methyl]-1H-isoindole-1,3(2H)-dione from 2-[[(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-5-oxazolidinyl]methyl]-1H-isoindole-1,3(2H)-dione was carried out in the following steps: in a four-necked round-bottomed flask. Methanol (2900 mL), 2-[[(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-5-oxazolidinyl]methyl]-1H-isoindole-1,3(2H)-dione (290 g), and 40% aqueous methylamine solution (265 g) were added. The reaction mixture was stirred at 25 to 30 °C for 1 hour, then heated to 60 to 65 °C and maintained at that temperature for 4 hours. Upon completion of the reaction, the mixture was cooled to 25 to 30 °C, concentrated hydrochloric acid (290 mL, adjusted pH to 1-2) was added and stirring was continued for 30 minutes. The resulting solid was collected by filtration and washed with cold methanol (290 mL). The yield was 92.0%.

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