Triethylamine → (3aR,7aR)-7,7-diphenyl-2-[(S)-2-phenylbutyryl]-4-perhydroisoindolone

HRID 1029923

Reaktionsgleichung

Reaktionsgleichung von HRID 1029923
[C:1]1([C@H:7]([CH2:11][CH3:12])[C:8]([OH:10])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[C:14]1([C:20]2([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C@H:28]3[C@H: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)[C@H:28]3[C@H:24]([CH2:25][N:26]([C:8](=[O:10])[C@H:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[CH2:11][CH3:12])[CH2:27]3)[C:23](=[O:29])[CH2:22][CH2:21]2)[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 785329(S)-2-Phenylbutyric acidHCID 22843247(3aR,7aR)-7,7-diphenyl-4-perhydroisoindolone hydrochloride

Produkt 1

HCID 22843245(3aR,7aR)-7,7-diphenyl-2-[(S)-2-phenylbutyryl]-4-perhydroisoindoloneAusbeute 41,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

N,N'-Carbonyldiimidazole (0.49 g) is added to a solution of (S)-2-phenylbutyric acid (0.5 g) in dry dichloromethane (15 cc), cooled to +5° C. The mixture is stirred for 30 minutes at +5° C. and a solution of (3aR,7aR)-7,7-diphenyl-4-perhydroisoindolone hydrochloride (0.98 g) and triethylamine (0.42 cc) in dichloromethane (20 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 chromatographed on a silica gel column (0.2-0.063 mm, diameter 1.6 cm, height 9.7 cm), eluting with a mixture of ethyl acetate and cyclohexane (80/20 by volume) and collecting 30 cc fractions. The first fraction is concentrated to dryness under reduced pressure (2.7 kPa). The residue is re-chromatographed on a silica gel column (0.2-0.063 mm, diameter 1.3 cm, height 14.5 cm), eluting with a mixture of cyclohexane and ethyl acetate (70/30 by volume) and collecting 50 cc fractions. Fractions 1 to 3 are combined and concentrated to dryness under reduced pressure (2.7 kPa). (3aR,7aR)-7,7-diphenyl-2-[(S)-2-phenylbutyryl]-4-perhydroisoindolone (0.54 g) is obtained in the form of a white meringue. [α]D20 =-216° (c=1, methanol).

Aufarbeitung

  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 chromatographed on a silica gel column (0.2-0.063 mm, diameter 1.6 cm, height 9.7 cm)
  8. washeluting with a mixture of ethyl acetate and cyclohexane (80/20 by volume)
  9. customcollecting 30 cc fractions
  10. concentrationThe first fraction is concentrated to dryness under reduced pressure (2.7 kPa)
  11. customThe residue is re-chromatographed on a silica gel column (0.2-0.063 mm, diameter 1.3 cm, height 14.5 cm)
  12. washeluting with a mixture of cyclohexane and ethyl acetate (70/30 by volume)
  13. customcollecting 50 cc fractions
  14. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Quellen und Nachweise

ORD-Eintrag
ord-501d8142fe1c4973b67ffea085237a8f
Quelldatensatz
uspto-grants-1992_04
Patentnummer
US05102667

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