New process for the synthesis of (3aS)-5,5-dioxo-2,3,3a,4-tetrahydro-1H- pyrrolo[2,1-c][1,2,4]benzothiadiazine

摘要

Process for the industrial synthesis of (3aS)-5,5-dioxo-2,3,3a,4-tetrahydro-1H-pyrrolo(2,1-c)(1,2,4)benzothiad iazine (I). Process for the industrial synthesis of (3aS)-5,5-dioxo-2,3,3a,4-tetrahydro-1H-pyrrolo(2,1-c)(1,2,4)benzothiad iazine (I) by hydrogenation of 5,5-dioxo-2,3-dihydro-1H-pyrrolo(2,1-c)(1,2,4)benzothiadiazine (II) in the presence of 0.4-2 mmoles of (R)BINAP RuCl2 (R,R) DPEN (III) per mole of (II) in 10-90 % toluene in isopropanol at a pressure of 4-25 bars, a temperature of 40-90 degrees C, and in the presence of 0.8-1.5 mole of a base such as potassium or sodium tertiary butanolate in an alcohol (e.g. tertiary butanol or isopropanol) per mole of (II). The compound is then isolated and recrystallized to give an isomeric excess over 80 %.