2-Methoxyphenylacetic acid → (3aRS,7aRS)-7,7-Bis(3-fluorophenyl)-2-(phenylacetyl)perhydro-4-isoindolone

Participants

Reaction Conditions

Reaction Steps

A solution of (2-methoxyphenyl)acetic acid (0.46 g) in dry dichloromethane (15 cc) is cooled to 0° C. and then treated with N,N'-carbonyldiimidazole (0.45 g) and stirred for 1 hour at 0° C. A solution of 7,7-bis-(3-fluorophenyl)-4-perhydroisoindolone hydrochloride (1 g) and triethylamine (0.76 cc) in dichloromethane (20 cc) is added dropwise. The reaction mixture is stirred for 3 hours at 25° C. and then washed with water (2×50 cc) and with saturated sodium chloride solution (50 cc). The organic phase is 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 (particle size 0.04-0.063 mm, diameter 2.2 cm, height 23 cm), eluting under a nitrogen pressure of 0.5 bar with a mixture of cyclohexane and ethyl acetate (70/30) and collecting 15 cc fractions. Fractions 4 to 9 are combined and concentrated to dryness under reduced pressure (2.7 kPa) and the product obtained is recrystallized from acetonitrile. The crystals are drained, washed with isopropyl ether and dried. (3aRS,7aRS)-7,7-bis-(3-fluorophenyl)-2-(phenylacetyl)-4-perhydroisoindolone (0.76 g) is obtained. m.p.=194° C.

Provenance & Evidence