Oxalic Acid → HCID 20065655, compound

Participants

Reaction Steps

60 cc of trifluoroacetic acid is added in the course of 45 minutes to 2-[3-(4-phenyl-1,2,3,6-tetrahydro-1pyridyl)propyl]-3-phenyl-3-hydroxy-1-isoindolinone (12.4 g) and sodium cyanoborohydride (3.8 g) cooled to a temperature close to -25° C. Agitation is continued for 2 hours at a temperature close to 20° C. The solution is diluted with methylene chloride (150 cc) then washed with saturated aqueous sodium bicarbonate solution (130 cc). The aqueous phase is extracted with methylene chloride (4×100 cc). The organic extracts are combined, washed with 1N hydrochloric acid solution (3×50 cc), dried over anhydrous magnesium sulphate, treated with animal charcoal, filtered and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C. The residue obtained is dissolved in tetrahydrofuran (150 cc). Tetramethylethylenediamine (4.5 cc) is added and the solution heated to a temperature close to 65° C. for 1 hour. After cooling to a temperature close to 20° C., the solution is diluted with methylene chloride (300 cc), washed with distilled water (5×50 cc). The organic extract is dried over anhydrous magnesium sulphate, filtered and evaporated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 50° C. The residue obtained is poured onto neutral alumina (750 g) contained in a column of 6 cm diameter. Elution is carried out with a mixture of ethyl acetate and cyclohexane (40-60 by volume) (2000 cc) and the corresponding eluates are eliminated. Elution is then carried out with ethyl acetate (3000 cc) and the corresponding eluates 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 (30 cc). A solution of oxalic acid (0.7 g) in methyl ethyl ketone (10 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 (240 cc). 1.6 g of 3-phenyl-2-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1-isoindolinone oxalate are obtained, melting at 198° C.

Provenance & Evidence