Triethylamine → HCID 67915912, compound

HRID 1029927Notes

Reaction equation

HRID 1029927 reaction equation
[C:1]1([CH:7]([C:18]([O-:20])=O)[C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[C:22]1([C:28]2([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[CH:36]3[CH:32]([CH2:33][NH:34][CH2:35]3)[C:31](=[O:37])[CH2:30][CH2:29]2)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(N(CC)CC)C>ClCCl>[CH2:11]([O:10][C:8]([CH:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C:18]([N:34]1[CH2:33][CH:32]2[CH:36]([C:28]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:29][CH2:30][C:31]2=[O:37])[CH2:35]1)=[O:20])=[O:9])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 212645437,7-Diphenylhexahydro-1H-isoindol-4(2H)-one hydrochlorideHCID 22140016Monobenzyl 2-phenylmalonate

Product 1

HCID 67915912HCID 67915912, compoundYield 2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N,N'-Carbonyldiimidazole (24.3 g) is added to a solution of monobenzyl phenylmalonate (40.5 g) in dry dichloromethane (810 cc), cooled to +5° C. The mixture is stirred for 25 minutes at +5° C. and a solution of (3aRS,7aRS)-7,7-diphenyl-4-perhydroisoindolone hydrochloride (49.1 g) and triethylamine (21 cc) in dichloromethane (1,000 cc) is then added. The reaction mixture is stirred at 20° C. for 16 hours, then washed with distilled water (3×1,000 cc), dried over magnesium sulphate and filtered and the filtrate is concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a silica gel column (0.2-0.063 mm, diameter 5.8 cm, height 63 cm), eluting with a mixture of ethyl acetate and cyclohexane (90/10 by volume) and collecting 200 cc fractions. Fractions 14 to 17 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized from isopropyl ether (400 cc); the crystals obtained are drained, washed with isopropyl ether (40 cc) and dried. The crystals obtained (5 g of the 35.6 g) are chromatographed on a silica gel column (0.2-0.063 mm, diameter 4.6 cm, height 30 cm), eluting with a mixture of cyclohexane and ethyl acetate (60/40 by volume) and collecting 100 cc fractions. Fractions 4 to 10 are combined and concentrated to dryness under reduced pressure (2.7 kPa); the residue is recrystallized from acetonitrile (5 cc). The crystals obtained are drained, washed with isopropyl ether (5 cc) and dried. (3aRS,7aRS)-2-(2-benzyloxycarbonyl-2-phenylacetyl)-7,7-diphenyl-4-perhydroisoindolone (1.6 g) melting at 210° C. is obtained.

Workup

  1. temperaturecooled to +5° C
  2. stirringThe reaction mixture is stirred at 20° C. for 16 hours
  3. washwashed with distilled water (3×1,000 cc)
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationthe filtrate is concentrated to dryness under reduced pressure (2.7 kPa)
  7. customThe residue is chromatographed on a silica gel column (0.2-0.063 mm, diameter 5.8 cm, height 63 cm)
  8. washeluting with a mixture of ethyl acetate and cyclohexane (90/10 by volume)
  9. customcollecting 200 cc fractions
  10. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  11. customThe residue is crystallized from isopropyl ether (400 cc)
  12. customthe crystals obtained
  13. washwashed with isopropyl ether (40 cc)
  14. customdried
  15. customThe crystals obtained (5 g of the 35.6 g)
  16. customare chromatographed on a silica gel column (0.2-0.063 mm, diameter 4.6 cm, height 30 cm)
  17. washeluting with a mixture of cyclohexane and ethyl acetate (60/40 by volume)
  18. customcollecting 100 cc fractions
  19. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  20. customthe residue is recrystallized from acetonitrile (5 cc)
  21. customThe crystals obtained
  22. washwashed with isopropyl ether (5 cc)
  23. customdried

Sources & evidence

ORD record
ord-13419980eb2b407b95aef413a7368a03
Source dataset
uspto-grants-1992_04
Patent number
US05102667

Reaction notes

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