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

HRID 1267433Notes

Reaction equation

HRID 1267433 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.[F:11][C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=1)[CH2:15][Mg]Cl>>[F: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 178505696HCID 178505696, compound

Product 1

HCID 129700935-[4-(3-Fluoro-phenyl)-3-oxo-butyl]-pyrrolidin-2-oneYield 62.3%

Procedure

Analogous to the procedure described for Example 1A, Step A, tetrahydro-pyrrolizine-3,5-dione (2 g, 14 mmol) was reacted with 3-fluorobenzylmagnesium chloride (0.25M in Et2O, 62 mL, 15.5 mmol) over 2.5 h. Purification by medium pressure chromatography using a solvent gradient (1:1 hexanes:EtOAc to 2:1 EtOAc:hexanes to EtOAc to 2% MeOH in CH2Cl2 to 10% MeOH in CH2Cl2) provided 5-[4-(3-fluoro-phenyl)-3-oxo-butyl]-pyrrolidin-2-one (2.1730 g). 1H NMR (CDCl3) δ7.32-7.27 (m, 1H), 7.00-6.90 (m, 3H), 6.12 (bs, 1H), 3.69 (s, 2H), 3.59 (m, 1H), 2.52 (t, 2H), 2.30 (m, 2H), 2.19 (m, 1H), 1.75 (m, 2H), 1.65 (m, 1H).

Workup

  1. customPurification by medium pressure chromatography

Sources & evidence

ORD record
ord-e6aa4aabe6814f4c8d3395794421b575
Source dataset
uspto-grants-2003_04
Patent number
US06552067B2

Reaction notes

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