3-Aminopiperidine-2,6-dione hydrochloride → 2-(2,6-Dioxopiperidin-3-yl)-4-(3-hydroxy-4-methoxyphenylamino)-isoindole-1,3-dione
Reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:19]=[CH:18][CH:17]=[C:13]([C:14]([OH:16])=O)[C:12]=2[C:20]([OH:22])=O)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].Cl.[NH2:24][CH:25]1[CH2:31][CH2:30][C:29](=[O:32])[NH:28][C:26]1=[O:27]>N1C=CC=CC=1>[O:27]=[C:26]1[CH:25]([N:24]2[C:20](=[O:22])[C:12]3[C:13](=[CH:17][CH:18]=[CH:19][C:11]=3[NH:10][C:4]3[CH:5]=[CH:6][C:7]([O:8][CH3:9])=[C:2]([OH:1])[CH:3]=3)[C:14]2=[O:16])[CH2:31][CH2:30][C:29](=[O:32])[NH:28]1Participants
4
Procedure
A mixture of 3-(3-hydroxy-4-methoxyphenylamino)phthalic acid (0.60 g, 2.0 mmol) and rac-α-aminoglutarimide hydrochloride (0.33 g, 2.0 mmol) in pyridine (10 mL) was heated to reflux for 16 hours. The mixture was cooled and evaporated under vacuum. The residue was dissolved in ethyl acetate (150 mL), washed with dilute aqueous HCl (2×100 mL) and water (2×100 mL), was dried (MgSO4) and evaporated. The residue was triturated in 1:1 acetonitrile-water (15 mL) and filtered, and the resulting solid was washed with additional 1:1 acetonitrile-water and dried under high vacuum, providing 0.45 g of the product, in 58% yield: mp 225-227° C.; 1H NMR (DMSO-d6) δ 2.03-2.08 (m, 1H), 2.52-2.63 (m, 2H), 2.83-2.92 (m, 1H), 3.77 (s, 3H), 5.11 (dd, J=12.5 Hz, J=5.4 Hz, 1H), 6.69-6.76 (m, 2H), 6.94 (d, J=8.5 Hz, 1H), 7.14-7.23 (m, 2H), 7.56 (t, J=7.8 Hz, 1H), 8.15 (s, 1H), 9.21 (s, 1H), 11.13 (s, 1H); 13C NMR (DMSO-d6) δ 22.1, 31.0, 48.6, 55.9, 110.7, 111.5, 112.5, 113.0, 114.2, 118.8, 132.1, 132.3, 136.1, 144.2, 145.2, 147.2, 167.1, 168.4, 170.0, 172.8; Anal. calcd for C20H17N3O6: C, 60.76; H, 4.33; N, 10.63. Found: C, 60.76; H, 4.11; N, 10.42.