Ethanol → (3aRS,7aRS)-7,7-Diphenylperhydro-4-isoindolone

Participants

Reaction Steps

A solution of (RS)-6-aminomethyl-7,7-diphenyl-1,4-dioxaspiro[4.5]decane (1 g) in ethanol (2 cc) is added to a solution, brought to reflux, of paraformaldehyde (0.09 g) in 2% strength aqueous sulphuric acid solution (5 cc), and heating to reflux is continued for 48 hours. The reaction mixture is then cooled to +5° C., alkalinized with 4N aqueous sodium hydroxide solution and extracted with dichloromethane (3×50 cc), and the organic phases are combined, washed with distilled water (100 cc), dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The residue is dissolved in acetone (8 cc), and this solution is acidified with 3.6N ethereal hydrogen chloride (2 cc) and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a column of silica gel with a slight excess pressure of nitrogen (0.04-0.063 mm, diameter 2.5 cm, height 35 cm), eluting with a mixture of dichloromethane and methanol (85:15) by volume) and collecting 15-cc fractions. Fraction 9 is concentrated to dryness under reduced pressure (2.7 kPa) and dissolved in water (10 cc), this aqueous solution is alkalinized at +5° C. with 4N aqueous sodium hydroxide solution and extracted with dichloromethane (3×30 cc), and the organic phases are combined, washed with distilled water (50 cc), dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure. (3aRS,7aRS)-7,7-Diphenylperhydro-4-isoindolone (0.07 g) is obtained in the form of a white meringue-like product.

Provenance & Evidence