Triethylamine → (3aRS,7aRS)-7,7-diphenyl-2-(2-hydroxyphenylacetyl)-4-perhydroisoindolone

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Reaction Steps

N,N'-Carbonyldiimidazole (1.14 g) is added to a solution, cooled to +5° C., of 2-hydroxyphenylacetic acid (1.06 g) in dry dichloromethane (30 cc). The mixture is stirred for 30 minutes at +5° C. and a solution of (3aRS,7aRS)-7,7-diphenylperhydro-4-isoindolone hydrochloride (2.23 g) and triethylamine (1.96 cc) in dichloromethane (20 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 4 cm, height 40 cm), eluting under a nitrogen pressure of 0.7 bar with a mixture of cyclohexane and ethyl acetate (70:30 by volume) and collecting 125-cc fractions. Fractions 4 to 11 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized in a mixture of acetonitrile (15 cc) and isopropyl ether (30 cc). The crystals are drained, washed with isopropyl ether and dried. (3aRS,7aRS)-7,7-Diphenyl-2-[(2-hydroxyphenyl)acetyl]perhydro-4-isoindolone (0.8 g) is obtained in the form of white crystals, m.p. 232° C.

Provenance & Evidence