[CH3:1][C:2]1([CH3:22])[O:6][C@@H:5]2[CH2:7][CH2:8][CH2:9][C@@H:10]([N:11]3C(=O)C4C(=CC=CC=4)C3=O)[C@@H:4]2[O:3]1.NN>C(O)C>[CH3:1][C:2]1([CH3:22])[O:6][C@@H:5]2[CH2:7][CH2:8][CH2:9][C@@H:10]([NH2:11])[C@@H:4]2[O:3]1The mixture of 2-[(3aS,4R,7aR)-2,2-dimethylhexahydro-1,3-benzodioxol-4-yl]-1H-isoindole-1,3(2H)-dione (20) (191.4 mmol, 50.00 g), hydrazine (308.4 mmol, 15.0 mL) in ethanol (500 mL) was refluxed for 4 h. The reaction was monitored by HPLC. HPLC analysis showed the reaction did not go to completion (86% conversion). Additional 3 mL of hydrazine was added to the reaction mixture and refluxed for 2 h. The reaction was cooled to 0° C. and filtered. The filter cake was washed with IPA and dried to afford the desired product 21 (9.52 g, 21% yield, purity in weight: 84% based on NMR). The filtrate was concentrated and the residue was taken up in IPA (about 200 mL). The by-product crystallized and was filtered out, and the filtrate was stripped of volatiles and dried to afford a second crop of the desired product 21(28.46 g, 64% yield). TLC (80% MeOH/EtOAc with 1 drop of acetic acid, stained by ninhydrin dip).
Loading…
