Dicyclohexylcarbodiimide → (3aR,7aR)-7,7-diphenyl-2-[(S)-2-methoxy-2-phenylacetyl]-4-perhydroisoindolone

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Reaction Steps

Hydroxybenzotriazole monohydrate (1 g) is added to a solution of (S)-α-methoxyphenylacetic acid (1.23 g) in dry dimethylformamide (20 cc), cooled to +5° C.; stirring is continued for 15 minutes and N,N'-dicyclohexylcarbodiimide (1.53 g) is then added. The mixture is stirred for 1 hour at +5° C. and a solution of (3aR,7aR)-7,7-diphenyl-4-perhydroisoindolone hydrochloride (2.43 g) and diisopropylethylamine (1.28 cc) in dry dimethylformamide (10 cc) is then added. The reaction mixture is stirred at +5° C. for 2 hours and then at ambient temperature for 2 hours. The reaction mixture, taken up in ethyl acetate (100 cc), is filtered; the filtrate is washed with distilled water (2×100 cc), dried over magnesium sulphate and filtered and the filtrate is concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a silica gel column (diameter 2.2 cm, height 27 cm), eluting with a mixture of cyclohexane and ethyl acetate (80/20 by volume) and collecting 20 cc fractions. Fractions 68 to 177 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized from isopropyl ether (15 cc); the crystals obtained are drained and then dried. (3aR,7aR)-7,7-diphenyl-2-[(S)-2-methoxy-2-phenylacetyl]-4-perhydroisoindolone (1.3 g) is obtained in the form of white crystals melting at 130° C.; [α]D20 =-230° (c=1, methanol).

Provenance & Evidence