2-Piperidone → 1-(3-Chloro-4-fluorobenzyl)piperidin-2-one

HRID 17983

Reaction equation

HRID 17983 reaction equation
[C:1]1(=[O:7])[NH:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[Cl:10][C:11]1[CH:12]=[C:13]([CH:16]=[CH:17][C:18]=1[F:19])[CH2:14]Br>CN1CCCC1=O>[Cl:10][C:11]1[CH:12]=[C:13]([CH:16]=[CH:17][C:18]=1[F:19])[CH2:14][N:6]1[CH2:5][CH2:4][CH2:3][CH2:2][C:1]1=[O:7]

Participants

5

Reactant 3

HCID 126652-PiperidoneHCID 24758Sodium hydrideHCID 27575424-(Bromomethyl)-2-chloro-1-fluorobenzene

Product 1

HCID 669976831-(3-Chloro-4-fluorobenzyl)piperidin-2-one

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

To a cold (0° C.) solution of valerolactam (153.30 g, 1.54 mol) in anhydrous 1-methyl-2-pyrrolidinone (3.5 L), sodium hydride (67.7 g, 1.69 mol, 60% dispersion in oil) was added over a period of 5 minutes. The reaction mixture was stirred for 30 minutes, and a solution of 3-chloro-4-fluorobenzylbromide (345.5 g, 1.54 mol) in 1-methyl-2-pyrrolidinone (200 mL) was added over 30 minutes at 0° C. The reaction mixture was stirred at 0° C. for 1 hour, and was allowed to warm up and stirred at room temperature overnight. The reaction mixture was quenched with distilled water (5 L), and extracted with dichloromethane (three times; 2 L, 1 L, 1 L). The organic extracts were combined, washed with water (3×; 4 L each time). The residual oil was dissolved in ethyl acetate (4 L), and extracted with water (3×; 2 L each time). The organic layer was separated, concentrated under vacuum to give the title product that solidified upon standing.

Workup

  1. stirringThe reaction mixture was stirred at 0° C. for 1 hour
  2. temperatureto warm up
  3. stirringstirred at room temperature overnight
  4. customThe reaction mixture was quenched with distilled water (5 L)
  5. extractionextracted with dichloromethane (three times; 2 L, 1 L, 1 L)
  6. washwashed with water (3×; 4 L each time)
  7. dissolutionThe residual oil was dissolved in ethyl acetate (4 L)
  8. extractionextracted with water (3×; 2 L each time)
  9. customThe organic layer was separated
  10. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-773d92763a474be5b2bc185f14e2f2dd
Source dataset
uspto-grants-2010_06
Patent number
US07741315B2

Linked notes

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