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

HRID 1196262Notes

Reaction equation

HRID 1196262 reaction equation
[NH2:1][CH2:2][CH:3]1[C:12]([C:19]2[CH:24]=C[CH:22]=[CH:21][CH:20]=2)([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:11]C[CH2:9][C:4]21OCCO2.[CH2:25]=O.S(=O)(=O)(O)O.[OH-].[Na+].[CH2:34]([OH:36])[CH3:35]>>[C:13]1([C:12]2([C:19]3[CH:20]=[CH:21][CH:22]=[CH:25][CH:24]=3)[CH:3]3[CH:4]([CH2:9][NH:1][CH2:2]3)[C:34](=[O:36])[CH2:35][CH2:11]2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 5

HCID 702EthanolHCID 712FormaldehydeHCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 54370231HCID 54370231, compound

Product 1

HCID 21264544(3aRS,7aRS)-7,7-Diphenylperhydro-4-isoindolone

Procedure

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.

Workup

  1. temperatureheating
  2. temperatureto reflux
  3. temperatureThe reaction mixture is then cooled to +5° C.
  4. extractionextracted with dichloromethane (3×50 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. dissolutionThe residue is dissolved in acetone (8 cc)
  10. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  11. customThe 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)
  12. washeluting with a mixture of dichloromethane and methanol (85:15) by volume) and
  13. customcollecting 15-cc fractions
  14. concentrationFraction 9 is concentrated to dryness under reduced pressure (2.7 kPa)
  15. dissolutiondissolved in water (10 cc)
  16. customis alkalinized at +5° C. with 4N aqueous sodium hydroxide solution
  17. extractionextracted with dichloromethane (3×30 cc)
  18. washwashed with distilled water (50 cc)
  19. dry with materialdried over magnesium sulphate
  20. filtrationfiltered
  21. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-2d2c66b05d644d4482bd57e97c152b27
Source dataset
uspto-grants-1992_05
Patent number
US05112988

Reaction notes

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