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

1. Process for the industrial synthesis of (3aS)-5,5-dioxo-2,3,3a,4-tetrahydro-1H-pyrrolo-[2,1-c][1,2,4]benzothiadiazine of formula (I): characterised in that 5,5-dioxo-2,3-dihydro-1H-pyrrolo[2,1-c][1,2,4]benzothiadiazine of formula (II): is hydrogenated in the presence of the catalyst (R)-BINAP RuCl2(R,R)-DPEN of formula (III): in an amount of from 0.4 to 2 mmol per mol of compound of formula (II), - in a mixture of toluene and isopropanol wherein the proportion of toluene is from 10 to 90% by volume, - under hydrogen pressure of from 4 to 25 bar, - at a temperature of from 40 to 90 degree C, - and in the presence of a base such as, for example, potassium or sodium tert-butoxide dissolved in an alcoholic solvent such as, for example, tert-butanol or isopropanol, in an amount of from 0.8 to 1.5 mol per mol of compound of formula (I), to yield directly, after isolation and then recrystallisation, the compound of formula (I) having an enantiomeric excess of more than 80 %. 2. Process according to claim 1, characterised in that the proportion of toluene in the toluene/isopropanol mixture is from 70 to 80 % by volume. 3. Process according to either claim 1 or claim 2, characterised in that the hydrogen pressure is from 10 to 15 bar. 4. Process according to any one of claims 1 to 3, characterised in that the hydrogenation temperature is from 65 to 75 degree C. 5. Process according to any one of claims 1 to 4, characterised in that the amount of base used is from 1 to 1.2 mol per mol of compound of formula (I).