Phthalimide → 2-[(1S)-3-Chloro-1-Phenylpropyl]-1H-Isoindole-1,3(2H)-Dione
Reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.[Cl:32][CH2:33][CH2:34][C@H:35]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)O.[C:43]1(=[O:53])[NH:47][C:46](=[O:48])[C:45]2=[CH:49][CH:50]=[CH:51][CH:52]=[C:44]12>C1COCC1>[Cl:32][CH2:33][CH2:34][C@H:35]([N:47]1[C:43](=[O:53])[C:44]2[C:45](=[CH:49][CH:50]=[CH:51][CH:52]=2)[C:46]1=[O:48])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
Triphenylphosphine (5.25 g, 20.0 mmol) and diethyl azodicarboxylate (3.58 g, 20.0 mmol) were added to a solution of (1R)-3-chloro-1-phenyl-1-propanol (3.42 g, 20.0 mmol) and phthalimide (2.94 g, 20.0 mmol) in THF (100 mL). The reaction mixture was stirred for 4 h at room temperature. The solvent was removed under reduced pressure and the residue was triturated with pentane (3×50 mL). The combined pentane fractions were concentrated in vacuo and the crude product was purified by chromatography on silica using EtOAc/hexane (3:97) to give the desired product (4.40 g, 74%). 1H NMR (400 MHz, CDCl3) δ 7.82 (d, 1H, J=5.7 Hz), 7.81 (d, 1H, J=5.5 Hz), 7.70 (d, 1H, J=5.4 Hz), 7.69 (d, 1H, J=5.8 Hz), 7.55 (d, 2H, J=7.2 Hz), 7.38-7.28 (m, 3H), 5.64 (dd, 1H, J=6.8, 9.2 Hz), 3.56 (t, 2H, J=6.4 Hz), 3.11-3.02 (m, 1H) 2.85-2.75 (m, 1H); ESMS m/e: 300.1 (M+H)+.
Workup
- customThe solvent was removed under reduced pressure
- customthe residue was triturated with pentane (3×50 mL)
- concentrationThe combined pentane fractions were concentrated in vacuo
- customthe crude product was purified by chromatography on silica
Sources & evidence
- ORD record
- ord-9ff67a5285ca4cb7ba1e818551154371
- Source dataset
- uspto-grants-2004_04
- Patent number
- US06727264B1
Reaction notes
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