Triethylamine → HCID 131717268, compound

HRID 1029895Notes

Reaction equation

HRID 1029895 reaction equation
[CH3:1][S:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]([OH:12])=O.Cl.[C:14]1([C:20]2([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH:28]3[CH:24]([CH2:25][NH:26][CH2:27]3)[C:23](=[O:29])[CH2:22][CH2:21]2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(N(CC)CC)C>ClCCl>[C:30]1([C:20]2([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:28]3[CH:24]([CH2:25][N:26]([C:10](=[O:12])[CH2:9][C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[S:2][CH3:1])[CH2:27]3)[C:23](=[O:29])[CH2:22][CH2:21]2)[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 12533891[2-(Methylsulfanyl)phenyl]acetic acidHCID 212645437,7-Diphenylhexahydro-1H-isoindol-4(2H)-one hydrochloride

Product 1

HCID 131717268HCID 131717268, compoundYield 59.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N,N'-Carbonyldiimidazole (0.77 g) is added to a solution of 2-methylthiophenylacetic acid (0.87 g) in dry dichloromethane (30 cc), cooled to +5° C. The mixture is stirred for 15 minutes at +5° C. and a solution of (3aRS,7aRS)-7,7-diphenyl-4-perhydroisoindolone hydrochloride (1.56 g) and triethylamine (1.34 cc) in dichloromethane (30 cc) is then added. The reaction mixture is stirred at 20° C. for 3.5 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 (0.04-0.063 mm, diameter 5 cm, height 50 cm), eluting under a nitrogen pressure of 0.5 bar with a mixture of cyclohexane and ethyl acetate (60/40 by volume) and collecting 50 cc fractions. Fractions 1 to 14 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The solid obtained is recrystallized from acetonitrile (5 cc) and the crystals are drained, washed with isopropyl ether and dried. (3aRS,7aRS)-7,7-diphenyl-2-[(2-methylthiophenyl)acetyl]-4-perhydroisoindolone (1.29 g) is obtained in the form of pale yellow crystals melting at 188° C.

Workup

  1. temperaturecooled to +5° C
  2. stirringThe reaction mixture is stirred at 20° C. for 3.5 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 (0.04-0.063 mm, diameter 5 cm, height 50 cm)
  8. washeluting under a nitrogen pressure of 0.5 bar
  9. additionwith a mixture of cyclohexane and ethyl acetate (60/40 by volume)
  10. customcollecting 50 cc fractions
  11. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  12. customThe solid obtained
  13. customis recrystallized from acetonitrile (5 cc)
  14. washwashed with isopropyl ether
  15. customdried

Sources & evidence

ORD record
ord-2c0c5e92e7ca4bd2808e334472e51c9b
Source dataset
uspto-grants-1992_04
Patent number
US05102667

Reaction notes

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