Triethylamine → HCID 67915998, compound

HRID 1029928Notes

Reaction equation

HRID 1029928 reaction equation
[C:1]1([CH2:7][C:8](O)=[O:9])[CH2:6][CH:5]=[CH:4][CH2:3][CH:2]=1.Cl.[C:12]1([C:18]2([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH:26]3[CH:22]([CH2:23][NH:24][CH2:25]3)[C:21](=[O:27])[CH2:20][CH2:19]2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C>ClCCl>[C:1]1([CH2:7][C:8]([CH:25]2[CH:26]3[CH:22]([C:21](=[O:27])[CH2:20][CH2:19][C:18]3([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:23][NH:24]2)=[O:9])[CH2:6][CH:5]=[CH:4][CH2:3][CH:2]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 12662078HCID 12662078, compoundHCID 212645437,7-Diphenylhexahydro-1H-isoindol-4(2H)-one hydrochloride

Product 1

HCID 67915998HCID 67915998, compoundYield 81.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N,N'-Carbonyldiimidazole (3.6 g) is added to a solution of (cyclohexa-1,4-dien-1-yl)acetic acid (2.35 g) in dry dichloromethane (50 cc), cooled to +5° C. The mixture is stirred for 30 minutes at +5° C. and a solution of 7,7-diphenyl-4-perhydroisoindolone hydrochloride (6.55 g) and triethylamine (5.6 cc) in dichloromethane (30 cc) is then added. The reaction mixture is stirred for 1 hour at +5° C. and then for 16 hours at 20° C. and is washed with normal hydrochloric acid (150 cc) and an aqueous saturated sodium chloride solution (150 cc). The organic phase is 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 (particle size 0.2-0.063 mm, diameter 6 cm, height 30 cm), eluting under a nitrogen pressure of 0.5 bar with a mixture (3 liters) of cyclohexane and ethyl acetate (50/50) and then with ethyl acetate (2 liters) and collecting 100 cc fractions. Fractions 10 to 48 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The residue is recrystallized from acetonitrile (15 cc). The crystals are drained, washed with acetonitrile (5 cc) and isopropyl ether (25 cc) and dried. (3aRS,7aRS)-2-(cyclohexa-1,4-dien-1-yl)-acetyl-7,7-diphenyl-4-perhydroisoindolone (5.7 g) is obtained. m.p.=186° C.

Workup

  1. temperaturecooled to +5° C
  2. stirringThe reaction mixture is stirred for 1 hour at +5° C.
  3. waitfor 16 hours at 20° C.
  4. washis washed with normal hydrochloric acid (150 cc)
  5. dry with materialThe organic phase is dried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationthe filtrate is concentrated to dryness under reduced pressure (2.7 kPa)
  8. customThe residue is chromatographed on a silica gel column (particle size 0.2-0.063 mm, diameter 6 cm, height 30 cm)
  9. washeluting under a nitrogen pressure of 0.5 bar with a mixture (3 liters) of cyclohexane and ethyl acetate (50/50)
  10. customwith ethyl acetate (2 liters) and collecting 100 cc fractions
  11. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  12. customThe residue is recrystallized from acetonitrile (15 cc)
  13. washwashed with acetonitrile (5 cc) and isopropyl ether (25 cc)
  14. customdried

Sources & evidence

ORD record
ord-83bb3278bf9d423a93218cb91c74cd8f
Source dataset
uspto-grants-1992_04
Patent number
US05102667

Reaction notes

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