Methanesulfonic Acid → 5-Amino-2,3-dihydro-isoindol-1-one

HRID 840866

Reaktionsgleichung

Reaktionsgleichung von HRID 840866
[NH2:1][C:2]1[CH:3]=[CH:4]C=[C:6]2[C:11](=O)[NH:10]C(=O)[C:7]=12.CS(O)(=O)=O.[C:18](O)([C:20](F)(F)F)=[O:19]>[Pd]>[NH2:1][C:2]1[CH:7]=[C:6]2[C:20](=[CH:4][CH:3]=1)[C:18](=[O:19])[NH:10][CH2:11]2

Komponenten

5

Edukt 3

HCID 6395Methanesulfonic AcidHCID 6422Trifluoroacetic acidHCID 729141H-Isoindole-1,3(2H)-dione, 4-amino-

Produkt 1

HCID 219562395-Amino-2,3-dihydro-isoindol-1-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 23938PalladiumKatalysator

Versuchsvorschrift

A solution of 16.2 g (100 mmol) of 6-aminophthalimide, 9.6 g (100 mmol) of methanesulfonic acid, and 4.0 g of 10% Pd/C in 140 mL of TFA was hydrogenated overnight at 50 psi. The catalyst was filtered off and and the filtrate concentrated on a rotary evaporator. The residue was diluted with 70 mL of ice water, adjusted to pH 8 with K2CO3, and chilled in an ice bath. The resulting solid was filtered to give 6.7 g of a 5:4 ratio of 5-amino:6-amino lactam isomers. Recrystallization from hot ethanol/water afforded 1.45 g of undesired isomer. The filtrate was preabsorbed onto silica gel and chromatographed with TEA:MeOH:methylene chloride (1:2:47). The resulting solid was slurried in methylene chloride/MeOH and filtered to afford a low yield of 5-amino-2,3-dihydro-isoindol-1-one: 1H NMR (DMSO-d6): δ4.13 (s, 2H), 5.67 (s, 2H), 6.55 (dd, J=8.7, 1.9 Hz, 1H), 6.55 (d, J=1.9 Hz, 1H), 7.25 (d, J=8.7 Hz, 1H), 7.83 (s, 1H); APCI−MS m/z 149 (M+H)+.

Aufarbeitung

  1. filtrationThe catalyst was filtered off
  2. concentrationthe filtrate concentrated on a rotary evaporator
  3. additionThe residue was diluted with 70 mL of ice water
  4. temperaturechilled in an ice bath
  5. filtrationThe resulting solid was filtered
  6. customto give 6.7 g of a 5:4 ratio of 5-amino
  7. customRecrystallization from hot ethanol/water
  8. customafforded 1.45 g of undesired isomer
  9. customThe filtrate was preabsorbed onto silica gel
  10. customchromatographed with TEA:MeOH:methylene chloride (1:2:47)
  11. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-e3e2484cda0a4dffa0c7a73cd7cd2128
Quelldatensatz
uspto-grants-2002_04
Patentnummer
US06369086B1

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