反应详情

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): δ 4.13 (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)+.

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