Triethylamine → (3aRS,7aRS)-2-[(2,6-difluorophenyl)acetyl]-7,7-diphenyl-4-perhydroisoindolone

HRID 1029876

Reaction equation

HRID 1029876 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=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>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[CH2:9][C:10]([N:26]1[CH2:25][CH:24]2[CH:28]([C:20]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:21][CH2:22][C:23]2=[O:29])[CH2:27]1)=[O:12]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 1235852,6-Difluorophenylacetic acidHCID 212645437,7-Diphenylhexahydro-1H-isoindol-4(2H)-one hydrochloride

Product 1

HCID 67916053(3aRS,7aRS)-2-[(2,6-difluorophenyl)acetyl]-7,7-diphenyl-4-perhydroisoindoloneYield 67.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N,N'-Carbonyldiimidazole (1.13 g) is added to a solution of 2-(2,6-difluorophenyl)acetic acid (1.2 g) in dry dichloromethane (30 cc), cooled to +5° C. The mixture is stirred for 45 minutes at +5° C. and a solution of (3aRS,7aRS)-7,7-diphenyl-4-perhydroisoindolone hydrochloride (2.3 g) and triethylamine (0.98 cc) in dichloromethane (40 cc) is then added. The reaction mixture is stirred at 20° C. for 16 hours, then washed with distilled water (2×50 cc), dried over magnesium sulphate and filtered and the filtrate is concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized from ethyl acetate (10 cc). The crystals obtained are drained, washed with isopropyl ether (10 cc) and dried. (3aRS,7aRS)-2-[(2,6-difluorophenyl)acetyl]-7,7-diphenyl-4-perhydroisoindolone (2.1 g) melting at 218° C. is obtained.

Workup

  1. temperaturecooled to +5° C
  2. stirringThe reaction mixture is stirred at 20° C. for 16 hours
  3. washwashed with distilled water (2×50 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 crystallized from ethyl acetate (10 cc)
  8. customThe crystals obtained
  9. washwashed with isopropyl ether (10 cc)
  10. customdried

Sources & evidence

ORD record
ord-9ab419e893b24617b15522ad16424269
Source dataset
uspto-grants-1992_04
Patent number
US05102667

Linked notes

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