Hydrochloric Acid → 3-(5-(aminomethyl)-1-oxo-2,3-dihydro-1H-isoindol-2-yl)piperidine-2,6-dione hydrochloride
Reaction equation
[O:1]=[C:2]1[CH:7]([N:8]2[CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:17]#[N:18])[CH:14]=3)[C:9]2=[O:19])[CH2:6][CH2:5][C:4](=[O:20])[NH:3]1.[ClH:21]>CN1CCCC1=O.[Pd]>[ClH:21].[NH2:18][CH2:17][C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:19])[N:8]([CH:7]1[CH2:6][CH2:5][C:4](=[O:20])[NH:3][C:2]1=[O:1])[CH2:16]2Participants
Procedure
A mixture of 2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindole-5-carbonitrile (9.2 g, 34 mmol), 10% Pd—C (1.7 g) and concentrated HCl (5.3 g) in N-methylpyrrolidone (300 mL) was hydrogenated at 58 psi overnight. The crude reaction mixture was filtered through Celite, and the catalyst washed with water. The combined filtrate was concentrated in vacuo, and the product, 3-(5-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hydrochloride, was isolated by fractional crystallization of the residue from isopropanol-water (1.9 g, 18%); 1H NMR (DMSO-d6) δ 1.85-2.20 (m, 1H), 2.35-2.45 (m, 1H), 2.58-2.80 (m, 1H), 2.87-2.99 (m, 1H), 4.16 (s, 2H), 4.35 (d, J=17.5 Hz, 1H), 4.49 (d, J=17.5 Hz, 1H), 5.13 (dd, J=13.2 Hz, J=4.8 Hz, 1H), 7.63 (d, J=7.8 Hz, 1H), 7.72 (s, 1H), 7.79 (d, J=7.8 Hz, 1H), 8.43 (br, 3H), 11.01 (s, 1H).
Workup
- customwas hydrogenated at 58 psi overnight
- customThe crude reaction mixture
- filtrationwas filtered through Celite
- washthe catalyst washed with water
- concentrationThe combined filtrate was concentrated in vacuo
Sources & evidence
- ORD record
- ord-f283badf356c470d9329c15316313f20
- Source dataset
- uspto-grants-2014_11
- Patent number
- US08877780B2
Reaction notes
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