Ammonia → HCID 20065654, compound

Participants

Reaction Steps

The same procedure is followed as in Example 2, but starting from an agitated solution of 2-[3-(4-(4-chlorophenyl)-1-piperazinyl)propyl-3-hydroxy-1-isoindolinone (4.8 g) in methanol (115 cc) to which 22.6 cc of concentrated sulphuric acid is added at a temperature close to 20° C. and in the course of 10 minutes. Agitation is continued for 5 hours at a temperature close to 65° C. After cooling the solution to a temperature close to 0° C., 55 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 33% aqueous solution of ammonia (50cc), and extracted with methylene chloride (3×200 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 8 cm diameter. Elution is carried out with a mixture of methylene chloride and methanol (98.5-1.5 by volume). The first 100 cc are eliminated and the next 630 cc are evaporated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 50° C. The residue obtained is dissolved in acetonitrile (30 cc). A solution of oxalic acid (0.63 g) in acetonitrile (15 cc) is added and agitation is continued for 1 hour at a temperature close to 20° C. The precipitate formed is separated by filtration. 2.9 g of 3-methoxy-2-[3-(4-(4-chlorophenyl)-1-piperazinyl)propyl]-1-isoindolinone oxalate are thus obtained, melting at 200° C.

Provenance & Evidence