Triethylamine → (3aR, 7aR)-2-[(RS)-2-(2-dimethylaminophenyl)propionyl]-7,7-diphenylperhydro-4-isoindolone

HRID 1196283Notes

Reaction equation

HRID 1196283 reaction equation
[CH3:1][N:2]([CH3:14])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH:9]([CH3:13])[C:10]([OH:12])=O.Cl.[C:16]1([C:22]2([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[C@H:30]3[C@H:26]([CH2:27][NH:28][CH2:29]3)[C:25](=[O:31])[CH2:24][CH2:23]2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(N(CC)CC)C>ClCCl>[CH3:14][N:2]([CH3:1])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH:9]([CH3:13])[C:10]([N:28]1[CH2:27][C@H:26]2[C@H:30]([C:22]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:23][CH2:24][C:25]2=[O:31])[CH2:29]1)=[O:12]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 22843247(3aR,7aR)-7,7-diphenyl-4-perhydroisoindolone hydrochlorideHCID 541006132-[2-(Dimethylamino)phenyl]propanoic acid

Product 1

HCID 22843227(3aR, 7aR)-2-[(RS)-2-(2-dimethylaminophenyl)propionyl]-7,7-diphenylperhydro-4-isoindoloneYield 58%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N,N'-carbonyldiimidazole (0.85 g) is added to a solution, cooled to 5° C., of (RS)-2-(2-dimethylaminophenyl)propionic acid (1 g) in dichloromethane (30 cc), and the mixture is stirred for 30 minutes at this temperature. A solution of (3aR, 7aR)-7,7-diphenylperhydro-4-isoindolone hydrochloride (1.7 g) and triethylamine (1.4 cc) in dichloromethane (30 cc) is added. The reaction mixture is stirred at 20° C. for 16 hours, washed with water (2×100 cc), dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a column of silica gel (0.2-0.063 mm, diameter 3 cm, height 50 cm), eluting under a nitrogen pressure of 0.5 bar with ethyl acetate and collecting 125-cc fractions. Fractions 4 to 6 are combined and concentrated to dryness under reduced pressure (2.7 kPa) to give (3aR, 7aR)-2-[(RS)-2-(2-dimethylaminophenyl)propionyl]-7,7-diphenylperhydro-4-isoindolone (1.4 g) in the form of white meringue-like product;

Workup

  1. stirringThe reaction mixture is stirred at 20° C. for 16 hours
  2. washwashed with water (2×100 cc)
  3. dry with materialdried over magnesium sulphate
  4. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  5. customThe residue is chromatographed on a column of silica gel (0.2-0.063 mm, diameter 3 cm, height 50 cm)
  6. washeluting under a nitrogen pressure of 0.5 bar with ethyl acetate
  7. customcollecting 125-cc fractions
  8. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-b910036bec7845c995a6e390a0a43b5a
Source dataset
uspto-grants-1992_05
Patent number
US05112988

Reaction notes

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