Triethylamine → (3aRS,7aRS)-7,7-bis-(2-fluorophenyl)-2-(2-dimethylaminophenyl)acetyl-4-perhydroisoindolone

Participants

Reaction Conditions

Reaction Steps

N,N-Carbonyldiimidazole (0.44 g) is added to a solution of (2-dimethylaminophenyl)acetic acid (0.49 g) in dry dichloromethane (20 cc) cooled to +4° C. The mixture is stirred for 1 hour at 25° C. and a solution of 7,7-bis-(2-fluorophenyl)-4-perhydroisoindolone hydrochloride (1 g) and triethylamine (0.76 cc) in dry dichloromethane (25 cc) is then added dropwise. The reaction mixture is stirred for 20 hours at 25° C. and washed with water (2×100 cc) and with saturated sodium chloride solution (100 cc). The organic phase is dried over magnesium sulphate and 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 cm, height 23 cm), eluting under a nitrogen pressure of 0.5 bar with a mixture of cyclohexane and ethyl acetate (50/50) and collecting 10 cc fractions. Fractions 14 to 36 are combined and concentrated to dryness under reduced pressure (2.7 kPa) to give (3aRS,7aRS)-7,7-bis-(2-fluorophenyl)-2-(2-dimethylaminophenyl)acetyl-4-perhydroisoindolone (1 g), from which the hydrochloride is prepared by dissolving in ethyl acetate (2 cc) and adding a 3N solution of hydrochloric acid in isopropyl ether. The precipitate is drained, washed with isopropyl ether and dried. (3aRS,7aRS)-7,7-bis-(2-fluorophenyl)-2-(2-dimethylaminophenyl)acetyl-4-perhydroisoindolone hydrochloride (0.87 g) is obtained in the form of a white solid.

Provenance & Evidence