2-[4-(Morpholin-4-yl)butyl]-1H-isoindole-1,3(2H)-dione → 4-(Morpholin-4-yl)butan-1-amine

Temperature

0 °C

A solution of phthalimide 307 (9.42 g, 32.7 mmol) and N2H4—H2O (3.2 mL, 65.3 mmol) in EtOH (140 mL) was stirred at reflux temperature for 2 h. The mixture was cooled to 0° C., filtered, the filtrate cooled at 0° C. for 3 h, and filtered. The filtrate was evaporated and the residue dissolved in 1 M HCl. The solution was washed with ether (2×50 mL) and the pH adjusted to 10 with aqueous NH3 solution. The resulting mixture was extracted with CHCl3 (4×50 mL), the combined organic fraction dried and the solvent evaporated to give diamine 308 (Thompson, A. M.; et. al., J. Med. Chem., 1997, 40, 3915-3925) (2.0 g, 39%) as a colourless oil: 1H NMR δ 3.72 (br t, J=4.7 Hz, 4H, 2×CH2O), 2.71 (br dd, J=6.9, 6.7 Hz, 2H, CH2N), 2.44 (br t, J=4.6 Hz, 4H, 2×CH2N), 2.34 (br dd, J=7.8, 7.0 Hz, 2H, CH2N), 1.62 (br s, 2H, NH2), 1.42-1.59 (m, 4H, 2×CH2)—

1. temperatureat reflux temperature for 2 h
2. filtrationfiltered
3. temperaturethe filtrate cooled at 0° C. for 3 h
4. filtrationfiltered
5. customThe filtrate was evaporated
6. dissolutionthe residue dissolved in 1 M HCl
7. washThe solution was washed with ether (2×50 mL)
8. extractionThe resulting mixture was extracted with CHCl3 (4×50 mL)
9. customthe combined organic fraction dried
10. customthe solvent evaporated

ORD record

ord-3bc3bbdf6fe8499c92a8c4b4de89b25b

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07989451B2