2-Methoxyphenylacetic acid → (3aR,7aR)-7,7-diphenyl-2-[(2-methoxyphenyl)acetyl]-4-perhydroisoindolone

Participants

Reaction Steps

N,N'-Carbonyldiimidazole (1 g) is added to a solution, cooled to +5° C., of 2-methoxyphenylacetic acid (1 g) in dry dichloromethane (30 cc). The mixture is stirred for 40 minutes at +5° C. and a solution of (3aR,7aR)-7,7-diphenylperhydro-4-isoindolone hydrochloride (2 g) and triethylamine (1.7 cc) in dichloromethane (40 cc) is then added. The reaction mixture is stirred at 20° C. for 16 hours, then washed with water (2×50 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 1.8 cm, height 13 cm), eluting with ethyl acetate and collecting 25-cc fractions. Fractions 3 to 5 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized in a mixture of acetonitrile (5 cc) and isopropyl ether (10 cc). The crystals are drained, washed with isopropyl ether (25 cc) and dried. (3aR,7aR)-(-)-7,7-Diphenyl-2-[(2-methoxyphenyl)acetyl]perhydro-4-isoindolone (1.7 g) is obtained in the form of white crystals, m.p. 200° C.; [α]D20 =-274° (c=0.49, acetic acid).

Provenance & Evidence