Triethylamine → (3aRS,7aRS)-7,7-diphenyl-2-(2-hydroxyphenylacetyl)-4-perhydroisoindolone

HRID 1196269Notes

Reaction equation

HRID 1196269 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([OH:11])=O.Cl.[C:13]1([C:19]2([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH:27]3[CH:23]([CH2:24][NH:25][CH2:26]3)[C:22](=[O:28])[CH2:21][CH2:20]2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(N(CC)CC)C>ClCCl>[C:29]1([C:19]2([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH:27]3[CH:23]([CH2:24][N:25]([C:9](=[O:11])[CH2:8][C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=4[OH:1])[CH2:26]3)[C:22](=[O:28])[CH2:21][CH2:20]2)[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 11970(2-Hydroxyphenyl)acetic acidHCID 212645437,7-Diphenylhexahydro-1H-isoindol-4(2H)-one hydrochloride

Product 1

HCID 67915856(3aRS,7aRS)-7,7-diphenyl-2-(2-hydroxyphenylacetyl)-4-perhydroisoindoloneYield 27.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N,N'-Carbonyldiimidazole (1.14 g) is added to a solution, cooled to +5° C., of 2-hydroxyphenylacetic acid (1.06 g) in dry dichloromethane (30 cc). The mixture is stirred for 30 minutes at +5° C. and a solution of (3aRS,7aRS)-7,7-diphenylperhydro-4-isoindolone hydrochloride (2.23 g) and triethylamine (1.96 cc) in dichloromethane (20 cc) is then added. The reaction mixture is stirred at 20° C. for 16 hours, then washed with water (2×100 cc), dried over magnesium sulphate, filtered 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 4 cm, height 40 cm), eluting under a nitrogen pressure of 0.7 bar with a mixture of cyclohexane and ethyl acetate (70:30 by volume) and collecting 125-cc fractions. Fractions 4 to 11 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized in a mixture of acetonitrile (15 cc) and isopropyl ether (30 cc). The crystals are drained, washed with isopropyl ether and dried. (3aRS,7aRS)-7,7-Diphenyl-2-[(2-hydroxyphenyl)acetyl]perhydro-4-isoindolone (0.8 g) is obtained in the form of white crystals, m.p. 232° C.

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. filtrationfiltered
  5. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  6. customThe residue is chromatographed on a column of silica gel (0.2-0.063 mm, diameter 4 cm, height 40 cm)
  7. washeluting under a nitrogen pressure of 0.7 bar
  8. additionwith a mixture of cyclohexane and ethyl acetate (70:30 by volume)
  9. customcollecting 125-cc fractions
  10. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  11. customThe residue is crystallized in a mixture of acetonitrile (15 cc) and isopropyl ether (30 cc)
  12. washwashed with isopropyl ether
  13. customdried

Sources & evidence

ORD record
ord-bdaafec9f2b14318891f533c5ca1026d
Source dataset
uspto-grants-1992_05
Patent number
US05112988

Reaction notes

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