Rolziracetam → 5-[4-(3-Chloro-phenyl)-3-oxo-butyl]-pyrrolidin-2-one

HRID 1267430Notes

Reaction equation

HRID 1267430 reaction equation
[CH2:1]1[CH:8]2[N:4]([C:5](=[O:9])[CH2:6][CH2:7]2)[C:3](=[O:10])[CH2:2]1.[Cl:11][C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=1)[CH2:15][Mg]Cl>>[Cl:11][C:12]1[CH:13]=[C:14]([CH2:15][C:5](=[O:9])[CH2:6][CH2:7][CH:8]2[NH:4][C:3](=[O:10])[CH2:2][CH2:1]2)[CH:18]=[CH:19][CH:20]=1

Participants

3

Reactant 2

HCID 71893RolziracetamHCID 178478996HCID 178478996, compound

Product 1

HCID 129700905-[4-(3-Chloro-phenyl)-3-oxo-butyl]-pyrrolidin-2-oneYield 51.5%

Procedure

Analogous to the procedure described for Example 1A, Step A, tetrahydro-pyrrolizine-3,5-dione (2 g, 14 mmol) was reacted with 3-chlorobenzylmagnesium chloride (0.25M in Et2O, 62 mL, 15.5 mmol) over 2 h. Purification by medium pressure chromatography eluting with a solvent gradient (2:1 hexanes:EtOAc to EtOAc to 5% MeOH in CH2Cl2) provided 5-[4-(3-chloro-phenyl)-3-oxo-butyl]-pyrrolidin-2-one (1.9142 g). 1H NMR (CDCl3) δ7.27 (m, 2H), 7.19 (m, 1H), 7.08 (m, 1H), 6.27 (br, 1H), 3.68 (s, 2H), 3.60 (m, 1H), 2.52 (t, 2H), 2.29 (m, 2H), 2.21 (m, 1H), 1.88-1.60 (m, 3H); MS 266.2 (M+1), 264.2 (M−1).

Workup

  1. customPurification by medium pressure chromatography
  2. washeluting with a solvent gradient (2:1 hexanes:EtOAc to EtOAc to 5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-adaa1217c84646b587aea8f206cbd016
Source dataset
uspto-grants-2003_04
Patent number
US06552067B2

Reaction notes

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