PROCEDURE FOR THE SYNTHESIS OF (3AS) -5,5-DIOXO-2,3,3A, 4-TETRAHIDRO-1H-PIRROLO (2,1-C) (1,2,4) BENZOTIADIAZINE.

摘要

Industrial synthesis procedure of (3aS) -5, 5-dioxo-2, 3, 3a, 4-tetrahydro-1H-pyrrolo [2, 1-c] [1, 2] 4 benzothiadiazine of Formula (I): * * (Formula) ** characterized in that 5, 5-dioxo-2, 3-dihydro-1H-pyrrolo [2, 1-c] [1, 2, 4] benzothiadiazine of Formula (II) is hydrogenated: ** (Formula ) ** in the presence of catalyst (R) BINAP RuCl2 (R, R) DPEN of Formula (III): ** (Formula) ** in an amount between 0.4 and 2 mmol per mole of compound of Formula (II ) - in a mixture of toluene and isopropanol in which the proportion of toluene is between 10 and 90% by volume, - under a hydrogen pressure between 4 and 25 bar, - at a temperature between 40 and 90 ° C, - and in the presence of a base such as, for example, potassium or sodium tert-butanolate dissolved in an alcoholic solvent such as, for example, tert-butanol or isopropanol, in an amount between 0, 8 and 1, 5 mol per mole of compound of Formula (II) for direct driving Then, after desparation and subsequent recrystallization, the compound of Formula (I) with an enantiomeric excess greater than 80%.