Triethylamine → HCID 67916012, compound

HRID 1029901Notes

Reaction equation

HRID 1029901 reaction equation
[CH2:1]([N:3]([CH2:14][CH3:15])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][C:11]([OH:13])=O)[CH3:2].Cl.[C:17]1([C:23]2([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH:31]3[CH:27]([CH2:28][NH:29][CH2:30]3)[C:26](=[O:32])[CH2:25][CH2:24]2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(N(CC)CC)C>ClCCl>[C:33]1([C:23]2([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:31]3[CH:27]([CH2:28][N:29]([C:11](=[O:13])[CH2:10][C:5]4[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=4[N:3]([CH2:1][CH3:2])[CH2:14][CH3:15])[CH2:30]3)[C:26](=[O:32])[CH2:25][CH2:24]2)[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 19899897HCID 19899897, compoundHCID 212645437,7-Diphenylhexahydro-1H-isoindol-4(2H)-one hydrochloride

Product 1

HCID 67916012HCID 67916012, compoundYield 63.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N,N'-Carbonyldiimidazole (0.86 g) is added to a solution of 2-diethylaminophenylacetic 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 (1.73 g) and triethylamine (1.48 cc) in dichloromethane (40 cc) is then added. The reaction mixture is stirred at 20° C. for 24 hours, then washed with water (2×150 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 40 cm), eluting under a nitrogen pressure of 0.7 bar with a mixture of cyclohexane and ethyl acetate (30/80 by volume) and collecting 125 cc fractions. Fractions 12 to 20 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized from a mixture of acetonitrile (15 cc) and isopropyl ether (50 cc). The crystals are drained, washed with isopropyl ether and dried. (3aRS,7aRS)-7,7-diphenyl-2-[2-(2-diethylaminophenyl)acetyl]-4-perhydroisoindolone (1.6 g) is obtained in the form of white crystals melting at 160° C.

Workup

  1. temperaturecooled to +5° C
  2. stirringThe reaction mixture is stirred at 20° C. for 24 hours
  3. washwashed with water (2×150 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 40 cm)
  8. washeluting under a nitrogen pressure of 0.7 bar
  9. additionwith a mixture of cyclohexane and ethyl acetate (30/80 by volume)
  10. customcollecting 125 cc fractions
  11. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  12. customThe residue is crystallized from a mixture of acetonitrile (15 cc) and isopropyl ether (50 cc)
  13. washwashed with isopropyl ether
  14. customdried

Sources & evidence

ORD record
ord-07cef118c7e6471f811161858f76b65b
Source dataset
uspto-grants-1992_04
Patent number
US05102667

Reaction notes

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