3-Pyridineacetic acid → HCID 67915794, compound

HRID 1029914Notes

Reaction equation

HRID 1029914 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][C:8]([OH:10])=O)[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:3]4[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=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 1083-Pyridineacetic acidHCID 8471TriethylamineHCID 212645437,7-Diphenylhexahydro-1H-isoindol-4(2H)-one hydrochloride

Product 1

HCID 67915794HCID 67915794, compoundYield 44.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N,N'-Carbonyldiimidazole (0.81 g) is added to a solution of 2-(3-pyridyl)acetic acid (0.685 g) in dry dichloromethane (15 cc), cooled to +5° C. The mixture is stirred for 30 minutes at +5° C. and a solution of (3aRS,7aRS)-7,7-diphenyl-4-perhydroisoindolone hydrochloride (1.6 g) and triethylamine (0.7 cc) in dichloromethane (10 cc) is then added. The reaction mixture is stirred at 20° C. for 16 hours and then concentrated to dryness under reduced pressure (2.7 kPa). The residue is taken up in a mixture of ethyl acetate (100 cc) and water (75 cc). The organic phase is washed with saturated sodium chloride solution (50 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 basic alumina column (diameter 2 cm, height 15 cm), eluting with ethyl acetate and collecting 50 cc fractions. Fractions 4 to 24 are concentrated to dryness under reduced pressure (2.7 kPa). The crystals obtained are recrystallized from acetonitrile (cc) to give (3aRS,7aRS)-7,7-diphenyl-2-[2-(3-pyridyl)acetyl]-4-perhydroisoindolone (0.9 g) in the form of white crystals melting at 208° C.

Workup

  1. temperaturecooled to +5° C
  2. stirringThe reaction mixture is stirred at 20° C. for 16 hours
  3. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  4. additionThe residue is taken up in a mixture of ethyl acetate (100 cc) and water (75 cc)
  5. washThe organic phase is washed with saturated sodium chloride solution (50 cc)
  6. dry with materialdried over magnesium sulphate
  7. filtrationfiltered
  8. concentrationthe filtrate is concentrated to dryness under reduced pressure (2.7 kPa)
  9. customThe residue is chromatographed on a basic alumina column (diameter 2 cm, height 15 cm)
  10. washeluting with ethyl acetate
  11. customcollecting 50 cc fractions
  12. concentrationFractions 4 to 24 are concentrated to dryness under reduced pressure (2.7 kPa)
  13. customThe crystals obtained
  14. customare recrystallized from acetonitrile (cc)

Sources & evidence

ORD record
ord-58b1d98392b5411ea19a61c5d0f5c027
Source dataset
uspto-grants-1992_04
Patent number
US05102667

Reaction notes

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