Ammonia → Simvastatin ammonium salt

Participants

Reaction Conditions

Reaction Steps

To the concentrate obtained in step 2 is added methanol (840 ml), water (550 ml) and sodium hydroxide (45 gm) at 25° C. The contents are heated to 75° C. and maintained for 7 hours at about 75° C. Then the solvent is distilled off at reduced pressure, cooled to 20° C. and water (400 ml) is added. Then the pH of the reaction mass is adjusted to 5 with 2N hydrochloric acid at 25° C., ethyl acetate (400 ml) is added and the pH is again adjusted to 3.5 with 2N hydrochloric acid solution. The layers are separated and the aqueous layer is washed with ethyl acetate (200 ml). The combined organic layer is dried on sodium sulfate. Ammonia solution, prepared by mixing aqueous ammonia (20 ml) and methanol (20 ml), is added to the reaction mass for 15 minutes at about 25° C., stirred for 1 hour at 25° C. and again for 1 hour at 0° C.–5° C. Then the separated solid is filtered and washed with chilled ethyl acetate (50 ml) to give 28 gm of simvastatin ammonium salt (HPLC Purity 97.5%).

Provenance & Evidence