Ammonia → HCID 20065670, compound

Participants

Reaction Steps

The same procedure is followed as in Example 2, but starting from an agitated solution of 2-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-3-hydroxy-1-isoindolinone (7 g) in ethanol (265 cc) to which 37 cc of concentrated sulphuric acid is added at a temperature close to 20° C. and in the course of 15 minutes. Agitation is continued for 4 hours at a temperature close to 65° C. After cooling the solution to a temperature close to 0° C., 90 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 (70 cc) and extracted with methylene chloride (3×250 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 (30 cc) and 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 (95-5 by volume). The first 1000 cc are eliminated, the next 900 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 (50 cc). A solution of oxalic acid (1.2 g) in methyl ethyl ketone (20 cc) is added and agitation is continued for 1 hour at a temperature close to 20° C. The precipitate formed is separated by filtration. 4.9 g of 3-ethoxy-2-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1-isoindolinone oxalate are thus obtained, melting at 150° C.

Provenance & Evidence