Potassium Carbonate → HCID 22843226, compound

HRID 1029961Notes

Reaction equation

HRID 1029961 reaction equation
F[B-](F)(F)F.O([O+](OCC)OCC)CC.[S:16]1[CH:20]=[CH:19][CH:18]=[C:17]1[CH2:21][NH:22][C:23](=O)[CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[O:31][CH3:32].Cl.[C:35]1([C:41]2([C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=3)[C@H:49]3[C@H:45]([CH2:46][NH:47][CH2:48]3)[C:44](=[O:50])[CH2:43][CH2:42]2)[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C(=O)([O-])[O-].[K+].[K+]>ClCCl.C(N(CC)CC)C>[CH3:32][O:31][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=1[CH2:24][C:23]([N:47]1[CH2:46][C@H:45]2[C@H:49]([C:41]([C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=3)([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[CH2:42][CH2:43][C:44]2=[O:50])[CH2:48]1)=[N:22][CH2:21][C:17]1[S:16][CH:20]=[CH:19][CH:18]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 6464944HCID 6464944, compoundHCID 14175583HCID 14175583, compoundHCID 22843247(3aR,7aR)-7,7-diphenyl-4-perhydroisoindolone hydrochloride

Product 1

HCID 22843226HCID 22843226, compoundYield 25.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

Triethoxyloxonium tetrafluoroborate (4 g) is added to a stirred solution of N-(2-thienyl)methyl-2-(2-methoxyphenyl)acetamide (5.2 g) in anhydrous dichloromethane (50 cc). Stirring of the reaction mixture is continued for 7 hours, at ambient temperature. The mixture is cooled to +5° C. and a solution of (3aR,7aR)-7,7-diphenyl-4-perhydroisoindolone hydrochloride (4.6 g) and triethylamine (5 cc) in dichloromethane (50 cc) is then added. Stirring of the reaction mixture is then continued for 20 hours at ambient temperature and the reaction mixture is then refluxed for 1 hour. It is then treated, after the temperature has returned to ambient temperature, with a 10% aqueous potassium carbonate solution (100 cc); the organic phase is washed with distilled water (40 cc), dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a Pechiney CBT1 neutral alumina gel column (diameter 5 cm, height 40 cm), eluting with a mixture of cyclohexane and ethyl acetate (50/50 by volume) and collecting 100 cc fractions. Fractions 4 to 13 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized from isopropanol (20 cc); the crystals obtained are drained, washed with isopropyl ether (10 cc) and dried. (3aR,7aR)-2-[2-(2-methoxyphenyl)-1-(2-thienylmethyl)iminoethyl]-7,7-diphenyl-4-perhydroisoindolone (1.9 g) melting at 88° C. is obtained; [α]D20 =-170° (c=1, methanol).

Workup

  1. temperatureThe mixture is cooled to +5° C.
  2. stirringStirring of the reaction mixture
  3. waitis then continued for 20 hours at ambient temperature
  4. temperaturethe reaction mixture is then refluxed for 1 hour
  5. additionIt is then treated
  6. washthe organic phase is washed with distilled water (40 cc)
  7. dry with materialdried over magnesium sulphate
  8. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  9. customThe residue is chromatographed on a Pechiney CBT1 neutral alumina gel column (diameter 5 cm, height 40 cm)
  10. washeluting with a mixture of cyclohexane and ethyl acetate (50/50 by volume)
  11. customcollecting 100 cc fractions
  12. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  13. customThe residue is crystallized from isopropanol (20 cc)
  14. customthe crystals obtained
  15. washwashed with isopropyl ether (10 cc)
  16. customdried

Sources & evidence

ORD record
ord-bab5012e632a4239ba4c52e06c250347
Source dataset
uspto-grants-1992_04
Patent number
US05102667

Reaction notes

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