Ammonia → HCID 20065653, compound

Participants

Reaction Steps

The same procedure is followed as in Example 2, but starting from an agitated solution of 3-hydroxy-2-[3-(4-(4-hydroxyphenyl)-1-piperazinyl)propyl]-1-isoindolinone (4.6 g) in methanol (115 cc), to which 22.7 cc of concentrated sulphuric acid is added in the course of 15 minutes and at a temperature close to 20° C. Agitation is continued for 5 hours at a temperature close to 65° C. After cooling the solution to a temperature close to 0° C., 57 cc of a 33% aqueous solution of ammonia is added in the course of 1 hour. The precipitate formed is filtered and washed with methanol (50 cc). The filtrate is diluted with distilled water (200 cc) and a 33% aqueous solution of ammonia (50 cc) and extracted with methylene chloride (4×100 cc). The organic extracts are combined, dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C. The residue obtained is dissolved in methylene chloride (20 cc) and the solution is poured onto silica (500 g) contained in a column of 6 cm diameter. Elution is carried out with a mixture of methylene chloride and methanol (97-3 by volume). The first 800 cc are eliminated and the next 3000 cc are evaporated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 50° C. The residue obtained is dissolved in methyl ethyl ketone (35 cc). A solution of oxalic acid (0.8 g) in methyl ethyl ketone (20 cc) is added, and agitation continued for 1 hour at a temperature close to 20° C. The precipitate formed is separated by filtration and recrystallized from boiling acetonitrile (200 cc). 1.4 g of 3-methoxy-2-[3-(4-(4-hydroxyphenyl)-1-piperazinyl)propyl]-1-isoindolinone oxalate are thus obtained, melting at 147° C.

Provenance & Evidence