Triethylamine → HCID 67915859, compound

HRID 1029896Notes

Reaction equation

HRID 1029896 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH2:15][C:16]([OH:18])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[C:20]1([C:26]2([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[CH:34]3[CH:30]([CH2:31][NH:32][CH2:33]3)[C:29](=[O:35])[CH2:28][CH2:27]2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(N(CC)CC)C>ClCCl>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH2:15][C:16]([N:32]1[CH2:31][CH:30]2[CH:34]([C:26]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:27][CH2:28][C:29]2=[O:35])[CH2:33]1)=[O:18])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 17890355{2-[(tert-Butoxycarbonyl)amino]phenyl}acetic acidHCID 212645437,7-Diphenylhexahydro-1H-isoindol-4(2H)-one hydrochloride

Product 1

HCID 67915859HCID 67915859, compoundYield 28.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N,N'-Carbonyldiimidazole (1.62 g) is added to a solution of (2-tert-butoxycarbonylaminophenyl)acetic acid (2.51 g) in dry dichloromethane (30 cc), cooled to +5° C. The mixture is stirred for 45 minutes at +5° C. and a solution of (3aRS,7aRS)-7,7-diphenyl-4-perhydroisoindolone hydrochloride (3.27 g) and triethylamine (2.8 cc) in dichloromethane (30 cc) is then added. The reaction mixture is stirred at 20° C. for 16 hours, then washed with water (3×100 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 4 cm, height 40 cm), eluting under a nitrogen pressure of 0.7 bar with a mixture of cyclohexane and ethyl acetate (60/40 by volume) and collecting 125 cc fractions. Fractions 22 to 34 are combined and concentrated to dryness under reduced pressure (2.7 kPa) to give (3aRS,7aRS)-2-[(2-tert-butoxycarbonylaminophenyl)acetyl]-7,7-diphenyl-4-perhydroisoindolone (1.5 g) in the form of a yellow meringue.

Workup

  1. temperaturecooled to +5° C
  2. stirringThe reaction mixture is stirred at 20° C. for 16 hours
  3. washwashed with water (3×100 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 4 cm, height 40 cm)
  8. washeluting under a nitrogen pressure of 0.7 bar
  9. additionwith a mixture of cyclohexane and ethyl acetate (60/40 by volume)
  10. customcollecting 125 cc fractions
  11. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-77fd9161af47461c99da63009c1b87b6
Source dataset
uspto-grants-1992_04
Patent number
US05102667

Reaction notes

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