Ethanol → (3aRS, 7aRS)-2-benzyl-7,7-diphenyl-4-perhydroisoindolone

HRID 1196256Notes

Reaction equation

HRID 1196256 reaction equation
[CH2:1]([NH:8][CH2:9][CH:10]1[C:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)(C2C=CC=CC=2)[CH2:18]C[CH2:16][C:11]21OCCO2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C=O.S(=O)(=O)(O)O.[OH-].[Na+].[CH2:41]([OH:43])[CH3:42]>>[CH2:1]([N:8]1[CH2:16][CH:11]2[CH:10]([C:19]([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH2:18][CH2:42][C:41]2=[O:43])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 5

HCID 702EthanolHCID 712FormaldehydeHCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 54379724HCID 54379724, compound

Product 1

HCID 19384608(3aRS, 7aRS)-2-benzyl-7,7-diphenyl-4-perhydroisoindolone

Procedure

A solution of (RS)-6-benzylaminomethyl-7,7-diphenyl-1,4-dioxaspiro[4.5]decane (0.41 g) in ethanol (0.4 cc) is added to a solution, brought to reflux, of paraformaldehyde (0.14 g) in 2% strength aqueous sulphuric acid solution (20 cc), and heating to reflux is continued for 48 hours. The reaction mixture is cooled to +25° C., alkalinized with 4N aqueous sodium hydroxide solution (5 cc) and extracted with ethyl acetate (4×40 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 chromatographed on a column of silica gel with a slight excess pressure of nitrogen (0.04-0.063 mm, diameter 2 cm, height 15 cm), eluting with a mixture of cyclohexane and ethyl acetate (60:40 by volume) and collecting 20-cc fractions. Fractions 4 and 5 are combined and concentrated to dryness under reduced pressure (2.7 kPa). (3aRS,7aRS)-2-Benzyl-7,7-diphenylperhydro-4-isoindolone (0.23 g) is obtained in the form of white crystals, m.p. 132° C.

Workup

  1. temperatureheating
  2. temperatureto reflux
  3. temperatureThe reaction mixture is cooled to +25° C.
  4. extractionextracted with ethyl acetate (4×40 cc)
  5. washwashed with distilled water (100 cc)
  6. dry with materialdried over magnesium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  9. customThe residue is chromatographed on a column of silica gel with a slight excess pressure of nitrogen (0.04-0.063 mm, diameter 2 cm, height 15 cm)
  10. washeluting with a mixture of cyclohexane and ethyl acetate (60:40 by volume)
  11. customcollecting 20-cc fractions
  12. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-e2a4eab44d4c4098adb95b673784c635
Source dataset
uspto-grants-1992_05
Patent number
US05112988

Reaction notes

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