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

HRID 2219683Notes

Reaction equation

HRID 2219683 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 Compound 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) δ 7.27 (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-05a0b573d9f1400cbadd1c1a8872e74a
Source dataset
uspto-grants-2008_08
Patent number
US07414071B2

Reaction notes

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