Phthalimide → 2-[(1S)-3-Chloro-1-Phenylpropyl]-1H-Isoindole-1,3(2H)-Dione

HRID 1269151Notes

Reaction equation

HRID 1269151 reaction equation
[C:1]1(=[O:11])[NH:5][C:4](=[O:6])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.[Cl:12][CH2:13][CH2:14][C@H:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[Cl:12][CH2:13][CH2:14][C@H:15]([N:5]1[C:1](=[O:11])[C:2]2[C:3](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:4]1=[O:6])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

6

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 642409(1R)-3-chloro-1-phenylpropan-1-ol

Product 1

HCID 207229752-[(1S)-3-Chloro-1-Phenylpropyl]-1H-Isoindole-1,3(2H)-DioneYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Prepared according to the general procedure described in Srebnik, M.; Ramachandran, P. V.; Brown, H. C. J. Org. Chem. 1988, 53, 2916–2920. A mixture of phthalimide (0.147 g, 1.0 mmol), (R)-(+)-3-chloro-1-phenyl-1-propanol (0.171 g, 1.0 mmol), triphenylphosphine (0.262 g, 1.0 mmol) and diethyl azodicarboxylate (0.174 g, 1.0 mmol) in 5.0 mL of THF was stirred at room temperature for 24 h. The reaction mixture was concentrated in vacuo. The residue was washed with pentane (3×50 mL) and the combined pentane extracts were concentrated and chromatographed (silica, hexanes: EtOAc=8:1 as the eluent) to give the desired product (0.121 g, 50%) as a yellow solid: 1H NMR (400 MHz, CDCl3) δ 7.82 (apparent dd, 2H, J=2.9 Hz), 7.70 (apparent dd, 2H, J=2.9 Hz), 7.56 (m, 2H), 7.39–7.27 (m, 3H), 5.64 (apparent dd, 1H, J=7.0, 9.2 Hz), 3.57 (m, 2H), 3.05 (m, 1H), 2.82 (septet, 1H, J=7.0 Hz); ESMS m/e: 300.1 (M+H)+.

Workup

  1. customPrepared
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. washThe residue was washed with pentane (3×50 mL)
  4. concentrationthe combined pentane extracts were concentrated
  5. customchromatographed (silica, hexanes

Sources & evidence

ORD record
ord-338b2a378c634ba996468a645fd18127
Source dataset
uspto-grants-2007_04
Patent number
US07199135B2

Reaction notes

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