Water → (3aRS,4RS,7aSR)-2-benzyl-4-[3,5-bis(trifluoromethyl)phenyl]-4-perhydroisoindolol

Participants

Reaction Conditions

Reaction Steps

To a solution of 3.06 cm3 of 3,5bis(trifluoromethyl)bromobenzene in 15 cm3 of dry tetrahydrofuran is added, at -78° C., a solution of 10.9 cm3 of 1.6M butyllithium in hexane. This solution is stirred for 30 minutes at -78° C., and a solution of 1 g of (3aRS,7aSR)-2-benzyl-4-perhydroisoindolone in 5 cm3 of tetrahydrofuran is then run in dropwise. The reaction mixture is subsequently stirred at room temperature for 18 hours, treated with 20 cm3 of water and then extracted with 20 cm3 of ethyl acetate. The organic phase is separated out after settling has taken place, washed with twice 20 cm3 of water, then with 20 cm3 of saturated sodium chloride solution, dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a column of silica gel (particle size 0.04-0.06 mm, diameter 2 cm, height 20 cm), eluting under a pressure of 0.5 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (90/10 by volume) and collecting 20 cm3 fractions. Fractions 26 to 37 are combined and then concentrated to dryness under reduced pressure (2.7 kPa). 0.82 g of (3aRS,4RS,7aSR)-2-benzyl-4-[3,5-bis(trifluoromethyl)phenyl]-4-perhydroisoindolol is obtained in the form of an oil.

Provenance & Evidence