Triphenylphosphine → 2-[[(2R)-4-[(3,4-Dichlorophenyl)methyl]morpholin-2-yl]methyl]isoindoline-1,3-dione

A mixture of 2-[(3,4-dichlorobenzyl)amino]ethanol (2.038 g) and (S)-2-(oxiran-2-ylmethyl)-1H-isoindole-1,3(2H)-dione (2.032 g) in tetrahydrofuran (3.3 ml) was stirred and heated at reflux under nitrogen. After 21.5 h more tetrahydrofuran (12.5 ml) was added and the mixture was cooled to 3°. Triphenyl phosphine (2.793 g) was added and the mixture was stirred until all the solid had dissolved. Diisopropylazodicarboxylate (2.1 ml) was then added over 12 min maintaining the temperature at <7°. After 2.25 h the mixture was allowed to warm to 22°. After 5.3 h more triphenylphosphine (121 mg) and diisopropylazodicarboxylate (0.09 ml) were added. After 22.5 h the reaction mixture was concentrated to near dryness. Propan-2-ol (12 ml) was added and the concentration repeated, this was repeated once more. More propan-2-ol (12 ml) was added and the mixture was heated to 70°. After 0.5 h the slurry was cooled to 22° and then after a further 2 h the product was collected. The bed was washed with propan-2-ol (2×4 ml) and then dried in vacuo at 40° to give the title compound (2.622 g).

1. temperatureheated
2. temperatureat reflux under nitrogen
3. temperaturethe mixture was cooled to 3°
4. stirringthe mixture was stirred until all the solid
5. dissolutionhad dissolved
6. temperaturemaintaining the temperature at <7°
7. temperatureto warm to 22°
8. concentrationAfter 22.5 h the reaction mixture was concentrated
9. additionPropan-2-ol (12 ml) was added
10. concentrationthe concentration
11. additionMore propan-2-ol (12 ml) was added
12. temperaturethe mixture was heated to 70°
13. temperatureAfter 0.5 h the slurry was cooled to 22°
14. customafter a further 2 h the product was collected
15. washThe bed was washed with propan-2-ol (2×4 ml)
16. customdried in vacuo at 40°

ORD 기록

ord-973dec614b7445bbbee6de54322fe380

출처 데이터셋

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07531651B2