Patent ID: 7179909
Filing Date: 2007-02-20
Classification: C07C

Abstract:
1. A process for preparing 2-imino-9-trifluoromethyl-4,5-dihydro-2H,7H-thiazolo[3,4,5-de][4,1]benzothiazepine 6,6-dioxide methanesulfonate wherein a) 4-trifluoromethylaniline is protected in the presence of di-tert-butyl dicarbonate in monochlorobenzene under reflux and then, b) the tert-butyl 4-trifluoromethylphenylcarbamate isolated in the preceding step is converted to 2-hydroxymethyl-4-trifluoromethylphenylcarbamate without isolating the intermediate 2-formyl-4-trifluoromethylphenylcarbamate, and then c) the 2-hydroxymethyl-4-trifluoromethylphenylcarbamate isolated in the preceding step is directly converted to 7-trifluoromethyl-1,5-dihydro-3H-[4,1]benzothiazepin-2-one in the presence of thioglycolic acid and a catalytic quantity of p-toluenesulfonic acid, and then d) the 7-trifluoromethyl-1,5-dihydro-3H-[4,1]benzothiazepin-2-one isolated in the preceding step is reduced in order to give 7-trifluoromethyl-1,2,3,5-tetrahydro-[4,1]benzothiazepine, and then e) 7-trifluoromethyl-1,2,3,5-tetrahydro-[4,1]benzothiazepine isolated in the preceding step is converted to 2-imino-9-trifluoromethyl-4,5-dihydro-2H,7H-thiazolo[3,4,5-de] [4,1]benzothiazepine hydrobromide in the presence of bromine, potassium thiocyanate in acetic acid, and then f) the 2-imino-9-trifluoromethyl-4,5-dihydro-2H,7H-thiazolo[3,4,5-de] [4,1]benzothiazepine hydrobromide is oxidized to 2-imino-9-trifluoromethyl-4,5-dihydro-2H,7H-thiazolo[3,4,5-de] [4,1]benzothiazepine 6,6-dioxide and is then converted in the presence of methanesulfonic acid to 2-imino-9-trifluoromethyl-4,5-dihydro-2H,7H-thiazolo[3,4,5-de] [4,1]benzothiazepine 6,6-dioxide methanesulfonate.