3-(Trifluoromethyl)benzyl chloride → 5-[3-Oxo-4-(3-trifluoromethyl-phenyl)-butyl]-pyrrolidin-2-one

HRID 458967Notes

Reaction equation

HRID 458967 reaction equation
[Mg].[O:2]=[C:3]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=1)[CH2:4][CH2:5][CH:6]1[NH:10][C:9](=[O:11])[CH2:8][CH2:7]1.FC(F)(F)C1C=C(C=CC=1)CCl.C1C2N(C(=O)CC2)C(=O)C1>CCOCC.C(Cl)Cl>[O:2]=[C:3]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:20])[F:21])[CH:14]=1)[CH2:4][CH2:5][CH:6]1[NH:10][C:9](=[O:11])[CH2:8][CH2:7]1

Participants

6

Reactant 3

HCID 697163-(Trifluoromethyl)benzyl chlorideHCID 71893RolziracetamHCID 692674185-[3-Oxo-4-(3-trifluoromethyl-phenyl)-butyl]-pyrrolidin-2-one Magnesium

Product 1

HCID 129700875-[3-Oxo-4-(3-trifluoromethyl-phenyl)-butyl]-pyrrolidin-2-one

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

5-[3-Oxo-4-(3-trifluoromethyl-phenyl)-butyl]-pyrrolidin-2-one Magnesium coils (1.13 g) were stirred under vacuum in a round bottom flask for 60 h. Anhydrous Et2O (5 mL) was added and the reaction mixture was cooled to 0° C. A solution of 3-trifluoromethylbenzyl chloride (1.0 mL, 7.5 mmol) in Et2O (25 mL) was added dropwise over 3 h. The reaction mixture was stirred for an additional 2.5 h. The solution was slowly added via a syringe and filtered through a Nylon Acrodisc™ syringe filter into a solution of tetrahydro-pyrrolizine-3,5-dione (650 mg, 4.68 mmol) in CH2Cl2 (30 mL) at 0° C. After 2 h, the reaction mixture was quenched with 1N HCl and the aqueous solution was washed with CH2Cl2 (2×). The organic solutions were combined, dried (MgSO4), filtered and concentrated. Medium pressure chromatography (1:1 hexanes:EtOAc) provided 5-[3-oxo-4-(3-trifluoromethyl-phenyl)-butyl]-pyrrolidin-2-one (1.376 g). 1H NMR (CDCl3) δ7.38 (m, 4H), 3.78 (s, 2H), 3.61 (m, 1H), 2.58 (t, 2H), 2.30 (m, 2H), 2.20 (m, 1H), 2.86–1.59 (m, 3H).

Workup

  1. stirringThe reaction mixture was stirred for an additional 2.5 h
  2. additionThe solution was slowly added via a syringe
  3. filtrationfiltered through a Nylon Acrodisc™ syringe
  4. waitAfter 2 h
  5. customthe reaction mixture was quenched with 1N HCl
  6. washthe aqueous solution was washed with CH2Cl2 (2×)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-e0fd25477971449ca0804d0cd61b715f
Source dataset
uspto-grants-2007_03
Patent number
US07192979B2

Reaction notes

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