Potassium Carbonate → HCID 22843225, compound

HRID 1029959Notes

Reaction equation

HRID 1029959 reaction equation
C([O+](CC)CC)C.[CH3:8][O:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH:16]([CH3:20])[C:17]([NH2:19])=O.Cl.[C:22]1([C:28]2([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[C@H:36]3[C@H: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(=O)([O-])[O-].[K+].[K+]>ClCCl.C(N(CC)CC)C>[NH:19]=[C:17]([N:34]1[CH2:33][C@H:32]2[C@H: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)[CH:16]([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=1[O:9][CH3:8])[CH3:20]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 165095TriethyloxoniumHCID 21262164HCID 21262164, compoundHCID 22843247(3aR,7aR)-7,7-diphenyl-4-perhydroisoindolone hydrochloride

Product 1

HCID 22843225HCID 22843225, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

Triethyloxonium tetrafluoborate (6.34 g) is added to a stirred suspension of (RS)-2-(2-methoxyphenyl)propionamide (5.4 g) in anhydrous dichloromethane (60 cc). The reaction mixture is stirred for 20 hours. A solution of (3aR,7aR)-7,7-diphenyl-4-perhydroisoindolone hydrochloride (6.65 g) and triethylamine (2.8 cc) in dichloromethane (30 cc) is added. The reaction mixture is refluxed for 5 hours. It is then cooled to +5° C. and is then treated with a 10% aqueous potassium carbonate solution (20 cc). After filtering, the organic phase is washed with distilled water (20 cc), dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a neutral alumina column (0.05 mm-0.160 mm, diameter 5 cm, height 20 cm), eluting with a mixture of cyclohexane and ethyl acetate (50/50) and collecting 250 cc fractions. The first fraction is concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a silica gel column (0.04 mm-0.06 mm, diameter 2 cm, height 35 cm), eluting with a mixture of n-butanol/acetic acid/pyridine/water (90/4/4/2 by volume) and collecting 20 cc fractions. Fractions 14 to 19 are concentrated to dryness under reduced pressure (0.13 kPa). The residue is taken up in dichloromethane (40 cc) and washed with aqueous potassium carbonate solution (10 cc). The organic phase is dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized from diisopropyl ether. The crystals are drained and dried under reduced pressure (0.13 kPa). (3aR,7aR)-2-[1-imino-2-(2-methoxyphenyl)-2-methylethyl]-7,7-diphenyl-4-perhydroisoindolone, form A, (0.12 g) is obtained in the form of a white meringue.

Workup

  1. temperatureThe reaction mixture is refluxed for 5 hours
  2. temperatureIt is then cooled to +5° C.
  3. filtrationAfter filtering
  4. washthe organic phase is washed with distilled water (20 cc)
  5. dry with materialdried over magnesium sulphate
  6. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  7. customThe residue is chromatographed on a neutral alumina column (0.05 mm-0.160 mm, diameter 5 cm, height 20 cm)
  8. washeluting with a mixture of cyclohexane and ethyl acetate (50/50)
  9. customcollecting 250 cc fractions
  10. concentrationThe first fraction is concentrated to dryness under reduced pressure (2.7 kPa)
  11. customThe residue is chromatographed on a silica gel column (0.04 mm-0.06 mm, diameter 2 cm, height 35 cm)
  12. washeluting with a mixture of n-butanol/acetic acid/pyridine/water (90/4/4/2 by volume)
  13. customcollecting 20 cc fractions
  14. concentrationFractions 14 to 19 are concentrated to dryness under reduced pressure (0.13 kPa)
  15. washwashed with aqueous potassium carbonate solution (10 cc)
  16. dry with materialThe organic phase is dried over magnesium sulphate
  17. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  18. customThe residue is crystallized from diisopropyl ether
  19. customdried under reduced pressure (0.13 kPa)

Sources & evidence

ORD record
ord-607560894d5d44a196bcdf3a60a20520
Source dataset
uspto-grants-1992_04
Patent number
US05102667

Reaction notes

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