(2S,3R)-Benzyl 2-((1,3-dioxoisoindolin-2-yl)methyl)-3-methylpiperidine-1-carboxylate → 2-(((2S,3R)-3-Methylpiperidin-2-yl)methyl)isoindoline-1,3-dione
Reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][C@@H:13]1[C@H:18]([CH3:19])[CH2:17][CH2:16][CH2:15][N:14]1C(OCC1C=CC=CC=1)=O>C(O)(=O)C.[Pd]>[CH3:19][C@@H:18]1[CH2:17][CH2:16][CH2:15][NH:14][C@@H:13]1[CH2:12][N:3]1[C:4](=[O:11])[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2]1=[O:1]Participants
4
Procedure
To a solution of (2S,3R)-benzyl 2-((1,3-dioxoisoindolin-2-yl)methyl)-3-methylpiperidine-1-carboxylate (14.2 g, 36.1 mmol) in acetic acid (40 ml) was added 10% Pd/C (1.5 g). The reaction was then stirred under H2 until HPLC indicated complete removal of the Cbz group. The reaction was the filtered through diatomaceous earth and concentrated. The crude residue was then dissolved in EtOAc and washed with saturated NaHCO3, brine, dried (MgSO4), and concentrated to yield the title compound as a yellow solid (8.2 g, 88%). 1H NMR (CDCl3, 400 MHz) δ 7.82-7.81 (m, 2H), 7.71-7.70 (m, 2H), 4.19-4.15 (m, 1H), 3.81-3.78 (m, 2H), 3.44 (m, 2H), 2.96 (m, 1H), 2.31 (m, 1H), 1.79-1.67 (m, 2H), 1.27 (d, J=4.0 Hz, 3H). ESI-MS (m/z): 259.2 [M+1]+.
Workup
- customremoval of the Cbz group
- filtrationfiltered through diatomaceous earth
- concentrationconcentrated
- dissolutionThe crude residue was then dissolved in EtOAc
- washwashed with saturated NaHCO3, brine
- dry with materialdried (MgSO4)
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-d4f08896988043eab95ae64699e32c3d
- Source dataset
- uspto-grants-2016_09
- Patent number
- US09440982B2
Reaction notes
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