反应详情

24 ml of a N solution of bromine in acetic acid were added to a solution of 2.28 g of 2,3-dihydro-3-(4-methoxy phenyl)-1,5-benzothiazepin-4(5H)-one of Step D of Example 1 in 16 ml of acetic acid. After 22 hours of stirring at ambient temperature, 100 ml of essence G were added and the gummy precipitate obtained was separated off by decanting the solution. Then, it was crystallized from 20 ml of ethanol and stirred for 30 minutes, followed by separation to obtain 2.22 g of the desired product melting at 200° C., then 220° C. The product was used as is for the following step. An analytical sample was prepared by dissolving 540 mg of the above product in 20 ml of methylene chloride and the solution was treated with activated charcoal and filtered. 50 ml of ethanol were added followed by concentration to 25 ml. After separating, 450 mg of product melting at 206° C., then 220° C. were obtained. The product was re-dissolved in 60 ml of ethanol at reflux, concentrated to 40 ml and separated after one night at ambient temperature to obtain 350 mg of the desired product melting at 210° C., then 220° C.

1. addition100 ml of essence G were added
2. customthe gummy precipitate obtained
3. customwas separated off
4. customby decanting the solution
5. customThen, it was crystallized from 20 ml of ethanol
6. stirringstirred for 30 minutes
7. customfollowed by separation