Ammonia → HCID 20065675, compound

Participants

Reaction Steps

The same procedure is followed as in Example 2, starting from an agitated solution of 2-[3-(4-(4-fluorophenyl)-1-piperazinyl)propyl]-3-hydroxy-1 -isoindolinone (6.8 g) in methanol (170 cc) to which 33.5 cc of concentrated sulphuric acid is added at a temperature close to 20° C. in the course of 15 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., 83 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 (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 (99-1 by volume). The first 300 cc are eliminated and the next 3500 cc are evaporated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 50° C. The residue obtained is dissolved in acetonitrile (50 cc). A solution of oxalic acid (1.1 g) in acetonitrile (25 cc) is added and agitation continued for 1 hour at a temperature close to 20° C. The precipitate formed is separated by filtration. 4.1 g of 3-methoxy-2-[3-(4-(4-fluorophenyl)-1-piperazinyl)propyl]-1-isoindolinone oxalate are thus obtained, melting at 177° C.

Provenance & Evidence