Ammonia → (3aR,7aR)-Octahydro-2-(1-imino-2-(2-methoxyphenyl)ethyl)-7,7-diphenyl-4H-isoindol-4-one

HRID 1029891Notes

Reaction equation

HRID 1029891 reaction equation
C([O+](CC)CC)C.[C:8]1([C:14]2([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[C@H:22]3[C@H:18]([CH2:19][N:20]([C:23](=O)[CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=4[O:31][CH3:32])[CH2:21]3)[C:17](=[O:34])[CH2:16][CH2:15]2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[NH3:41].C(=O)([O-])[O-].[K+].[K+]>ClCCl>[NH:41]=[C:23]([N:20]1[CH2:19][C@H:18]2[C@H:22]([C:14]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)([C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=3)[CH2:15][CH2:16][C:17]2=[O:34])[CH2:21]1)[CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[O:31][CH3:32]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 11430Potassium CarbonateHCID 165095TriethyloxoniumHCID 15182925(3aR,7aR)-7,7-diphenyl-2-[(2-methoxyphenyl)acetyl]-4-perhydroisoindolone

Product 1

HCID 107686(3aR,7aR)-Octahydro-2-(1-imino-2-(2-methoxyphenyl)ethyl)-7,7-diphenyl-4H-isoindol-4-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-15 °C

Procedure

Triethyloxonium tetrafluoborate (4 g) is added to a solution of (3aR,7aR)-7,7-diphenyl-2-[(2-methoxyphenyl)acetyl]-4-perhydroisoindolone (7.7 g) in anhydrous dichloromethane (13 cc). Stirring of the reaction mixture is continued for 20 hours at ambient temperature; the mixture is then cooled to -15° C. and a 5.4N ethanolic ammonia solution (2.6 cc) is then added. The temperature of the reaction mixture is allowed to rise to ambient temperature and stirring is continued for 5 hours and a half. The reaction mixture is treated with a 10% aqueous solution (20 cc) of potassium carbonate; the precipitate formed is drained and washed with dichloromethane (10 cc). The organic phases are combined, dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized from acetonitrile (10 cc); the crystals obtained are drained, washed with acetonitrile (5 cc) and with isopropyl ether (10 cc) and dried. They are then chromatographed on a Pechiney CBT1 neutral alumina gel column (diameter 4.5 cm, height 28 cm), eluting with a mixture (200 cc) of 1,2-dichloroethane and methanol (98/2 by volume) and then with a mixture of 1,2-dichloroethane and methanol (90/10 by volume), collecting 25 cc fractions. Fractions 8 to 31 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized from acetonitrile (10 cc); the crystals obtained are drained and dried. (3aR,7aR)-2-[1-imino-2-(2-methoxyphenyl)ethyl]-7,7-diphenyl-4-perhydroisoindolone (1.6 g) melting at 190° C. is obtained; [α]20D =-254° (c=1, methanol).

Workup

  1. customto rise to ambient temperature
  2. stirringstirring
  3. waitis continued for 5 hours
  4. customthe precipitate formed
  5. washwashed with dichloromethane (10 cc)
  6. dry with materialdried over magnesium sulphate
  7. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  8. customThe residue is crystallized from acetonitrile (10 cc)
  9. customthe crystals obtained
  10. washwashed with acetonitrile (5 cc) and with isopropyl ether (10 cc)
  11. customdried
  12. customThey are then chromatographed on a Pechiney CBT1 neutral alumina gel column (diameter 4.5 cm, height 28 cm)
  13. washeluting with a mixture (200 cc) of 1,2-dichloroethane and methanol (98/2 by volume)
  14. additionwith a mixture of 1,2-dichloroethane and methanol (90/10 by volume)
  15. customcollecting 25 cc fractions
  16. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  17. customThe residue is crystallized from acetonitrile (10 cc)
  18. customthe crystals obtained
  19. customdried

Sources & evidence

ORD record
ord-01d8ce25905b47de91de23a13b8e5d93
Source dataset
uspto-grants-1992_04
Patent number
US05102667

Reaction notes

Loading…