Triethylamine → HCID 19384619, compound

HRID 1029899Notes

Reaction equation

HRID 1029899 reaction equation
[CH3:1][N:2]([CH3:13])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]([OH:12])=O.Cl.[C:15]1([C:21]2([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH:29]3[CH:25]([CH2:26][NH:27][CH2:28]3)[C:24](=[O:30])[CH2:23][CH2:22]2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(N(CC)CC)C>ClCCl>[C:31]1([C:21]2([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:29]3[CH:25]([CH2:26][N:27]([C:10](=[O:12])[CH2:9][C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[N:2]([CH3:1])[CH3:13])[CH2:28]3)[C:24](=[O:30])[CH2:23][CH2:22]2)[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 204661092-(2-(Dimethylamino)phenyl)acetic acidHCID 212645437,7-Diphenylhexahydro-1H-isoindol-4(2H)-one hydrochloride

Product 1

HCID 19384619HCID 19384619, compoundYield 32.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N,N'-Carbonyldiimidazole (1 g) is added to a solution of 2-dimethylaminophenylacetic acid (1.1 g) in dry dichloromethane (30 cc), cooled to +5° C. The mixture is stirred at +5° C. for 30 minutes and a solution of (3aRS,7aRS)-7,7-diphenyl-4-perhydroisoindolone hydrochloride (2.03 g) and triethylamine (1.68 cc) in dichloromethane (20 cc) is then added. The reaction mixture is stirred at 20° C. for 24 hours, then washed with water (3×200 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 3 cm, height 25 cm), eluting under a nitrogen pressure of 0.7 bar with a mixture of cyclohexane and ethyl acetate (40/60 by volume) and collecting 125 cc fractions. Fractions 8 to 26 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized from isopropyl ether (40 cc). The crystals are drained, washed with isopropyl ether and dried. (3aRS,7aRS)-7,7-diphenyl-2-[2-(2-dimethylaminophenyl)acetyl]-4-perhydroisoindolone (0.9 g) is obtained in the form of white crystals melting at 150° C.

Workup

  1. temperaturecooled to +5° C
  2. stirringThe reaction mixture is stirred at 20° C. for 24 hours
  3. washwashed with water (3×200 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 3 cm, height 25 cm)
  8. washeluting under a nitrogen pressure of 0.7 bar
  9. additionwith a mixture of cyclohexane and ethyl acetate (40/60 by volume)
  10. customcollecting 125 cc fractions
  11. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  12. customThe residue is crystallized from isopropyl ether (40 cc)
  13. washwashed with isopropyl ether
  14. customdried

Sources & evidence

ORD record
ord-c76a1a440c504c739948bc4ce5430a3f
Source dataset
uspto-grants-1992_04
Patent number
US05102667

Reaction notes

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