Cerium(III) chloride → (3aRS,4RS,7aRS)-7,7-dimethyl-4-(2-methoxyphenyl)-2-[(2-methoxyphenyl)acetyl]2,3,3a,4,7,7a-hexahydro-1H-4-isoindolol

Participants

Reaction Conditions

Reaction Steps

To a suspension of 22.73 g of 2-methoxyphenylmagnesium bromide in 70 cm3 of tetrahydrofuran, cooled to 15° C., are added, dropwise and with stirring, a solution of 6.77 g of (3aRS,7aRS)7, 7-dimethyl-2-[(2-methoxyphenyl)acetyl]-2,3,3a,4,7,7a -hexahydro-1H-4-isoindolone in 10 cm3 of tetrahydrofuran, followed by 5.3 g of anhydrous cerium chloride. The reaction mixture is stirred at room temperature for 18 hours, treated with 80 cm3 of saturated aqueous ammonium chloride solution, taken up in 100 cm3 of ethyl acetate and washed with 100 cm3 of saturated aqueous sodium chloride solution. The organic phase is separated out after settling has taken place, 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 (particle size 0.04-0.06 mm, diameter 5.5 cm, height 30 cm), eluting under a pressure of 0.5 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (50/50 by volume) and collecting 75 cm3 fractions. Fractions 17 to 40 are combined and then concentrated to dryness under reduced pressure (2.5 kPa). 4.98 g of (3aRS,4RS,7aRS)-7,7-dimethyl-4-(2-methoxyphenyl)-2-[(2-methoxyphenyl)acetyl]2,3,3a,4,7,7a-hexahydro-1H-4-isoindolol are obtained in the form of a colourless oil.

Provenance & Evidence