Phenylacetic Acid → (3aRS,7aRS)-7,7-diphenyl-2-(phenylacetyl)-4-perhydroisoindolone

HRID 1029868Notes

Reaction equation

HRID 1029868 reaction equation
[C:1]1([CH2:7][C:8]([OH:10])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[C:12]1([C:18]2([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH:26]3[CH:22]([CH2:23][NH:24][CH2:25]3)[C:21](=[O:27])[CH2:20][CH2:19]2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C>ClCCl>[C:28]1([C:18]2([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:26]3[CH:22]([CH2:23][N:24]([C:8](=[O:10])[CH2:7][C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[CH2:25]3)[C:21](=[O:27])[CH2:20][CH2:19]2)[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1

Participants

5

Reactant 3

HCID 999Phenylacetic AcidHCID 8471TriethylamineHCID 212645437,7-Diphenylhexahydro-1H-isoindol-4(2H)-one hydrochloride

Product 1

HCID 67916161(3aRS,7aRS)-7,7-diphenyl-2-(phenylacetyl)-4-perhydroisoindoloneYield 67%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N,N'-Carbonyldiimidazole (1.7 g) is added to a solution of phenylacetic acid (1.34 g) in dry dichloromethane (30 cc) cooled to +5° C. The mixture is stirred for 1 hour at +5° C. and a solution of 7,7-diphenyl-4-perhydroisoindolone hydrochloride (3.27 g) and triethylamine (1.7 cc) in dichloromethane (30 cc) is then added. The reaction mixture is stirred for 1 hour at +5° C. and then for 1 hour at 20° C. The reaction mixture is washed with a saturated aqueous solution (50 cc) of sodium bicarbonate, dried over magnesium sulphate and filtered and the filtrate is concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized from acetonitrile (15 cc). The crystals are drained, washed with isopropyl ether (10 cc) and dried. (3aRS,7aRS)-7,7-diphenyl-2-(phenylacetyl)-4-perhydroisoindolone (2.7 g) melting at 216° C. is obtained.

Workup

  1. temperaturecooled to +5° C
  2. stirringThe reaction mixture is stirred for 1 hour at +5° C.
  3. waitfor 1 hour at 20° C
  4. washThe reaction mixture is washed with a saturated aqueous solution (50 cc) of sodium bicarbonate
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationthe filtrate is concentrated to dryness under reduced pressure (2.7 kPa)
  8. customThe residue is crystallized from acetonitrile (15 cc)
  9. washwashed with isopropyl ether (10 cc)
  10. customdried

Sources & evidence

ORD record
ord-5c3ef38f7888458aac459354f47d2c9d
Source dataset
uspto-grants-1992_04
Patent number
US05102667

Reaction notes

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