Triethylamine → (3aR, 7aR)-7,7-Diphenyl-2-[2(2-dimethylaminophenyl)acetyl]perhydro-4-isoindolone

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Reaction Steps

N,N'-carbonyldiimidazole (2.43 g) is added to a solution, cooled to +5° C., of 2-dimethylaminophenylacetic acid (2.68 g) in dry dichloromethane (50 cc). The mixture is stirred for 90 minutes at +5° C. and a solution of (3aR, 7aR)-7,7-diphenylperhydro-4-isoindolone hydrochloride (4.9 g) and triethylamine (4.2 cc) in dichloromethane (50 cc) is then added. The reaction mixture is stirred at 20° C. for 16 hours, then washed with water (2×100 cc), dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a column of silica gel (0.2-0.063 mm, diameter 5 cm, height 50 cm), eluting under a nitrogen pressure of 0.7 bar with a mixture of cyclohexane and ethyl acetate (40:60 by volume) and collecting 125-cc fractions. Fractions 5 to 20 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized in a mixture of acetonitrile (40 cc) and isopropyl ether (200 cc). The crystals are drained, washed with isopropyl ether and dried. (3aR, 7aR)-7,7-Diphenyl-2-[2(2-dimethylaminophenyl)acetyl]perhydro-4-isoindolone (2.58 g) is obtained in the form of white crystals, m.p. 190° C.; [α]D20 =-242° (c=1.18, chloroform).

Provenance & Evidence