Water → 1-(2,3-Difluorobenzyl)pyrrolidin-2-one

HRID 1912610Notes

Reaction equation

HRID 1912610 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][C:2]1=[O:6].[H-].[Na+].Br[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[C:12]=1[F:18].O>CN(C)C=O>[F:18][C:12]1[C:13]([F:17])=[CH:14][CH:15]=[CH:16][C:11]=1[CH2:10][N:1]1[CH2:5][CH2:4][CH2:3][C:2]1=[O:6]

Participants

6

Reactant 4

HCID 962WaterHCID 120252-PyrrolidoneHCID 24758Sodium hydrideHCID 5179841-(Bromomethyl)-2,3-difluoro-benzene

Product 1

HCID 712090031-(2,3-Difluorobenzyl)pyrrolidin-2-oneYield 71.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of pyrrolidin-2-one (9.38 mL, 121 mmol) in N,N-dimethylformamide (DMF) (200 mL) was added in portions sodium hydride (6.04 g, 151 mmol) (60%/mineral oil) in 10 min and the mixture was stirred under nitrogen atmosphere at ambient temperature for 2 h then 1-(bromomethyl)-2,3-difluorobenzene (15.37 mL, 121 mmol) was added dropwise over 15 min and the mixture was stirred at ambient temperature for 2.5 h. Water (600 mL) was added and the mixture was stirred at ambient temperature for 30 min then extracted with EtOAc. The organic phase was washed with water (3×), and brine, dried (Na2SO4), concentrated, dissolved in acetonitrile and washed with hexanes (2×). The acetonitrile phase was concentrated, dried in vacuo to provide 1-(2,3-difluorobenzyl)pyrrolidin-2-one (19.14 g, 86 mmol, 71.2% yield) as a yellowish oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.03 (quint, J=7.61 Hz, 2 H), 2.43 (t, J=8.10 Hz, 2 H), 3.34 (t, J=7.02 Hz, 2 H), 4.54 (s, 2 H), 6.99-7.17 (m, 3 H); LCMS (m/z) ES+=212 (M+1).

Workup

  1. stirringthe mixture was stirred at ambient temperature for 2.5 h
  2. stirringthe mixture was stirred at ambient temperature for 30 min
  3. extractionthen extracted with EtOAc
  4. washThe organic phase was washed with water (3×), and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. dissolutiondissolved in acetonitrile
  8. washwashed with hexanes (2×)
  9. concentrationThe acetonitrile phase was concentrated
  10. customdried in vacuo

Sources & evidence

ORD record
ord-a5e06e996ff5438d80e9646beb0a11c1
Source dataset
uspto-grants-2013_12
Patent number
US08609653B2

Reaction notes

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