N-Methylacetamide → N-[(4-Fluorophenyl)methyl]-N-methylacetamide

HRID 2053706Notes

Reaction equation

HRID 2053706 reaction equation
[H-].[Na+].[CH3:3][NH:4][C:5](=[O:7])[CH3:6].[F:8][C:9]1[CH:16]=[CH:15][C:12]([CH2:13]Br)=[CH:11][CH:10]=1>C1COCC1>[CH3:3][N:4]([CH2:13][C:12]1[CH:15]=[CH:16][C:9]([F:8])=[CH:10][CH:11]=1)[C:5](=[O:7])[CH3:6]

Participants

5

Reactant 3

HCID 6582N-MethylacetamideHCID 24758Sodium hydrideHCID 680214-Fluorobenzyl bromide

Product 1

HCID 21947447N-[(4-Fluorophenyl)methyl]-N-methylacetamideYield 95.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of NaH (6.86 g, 0.172 mole, 60% in mineral oil, 1.3 equiv) in THF (250 mL), add dropwise a solution of N-methylacetamide (11.6 g, 0.159 mole, 1.2 equiv) in THF (90 mL). After about 20 min, add 4-fluorobenzylbromide (25 g, 0.132 mole). Stir for about 62 hours then pour over ice water (300 mL) and extract with ethyl acetate (400 mL and 200 mL). Combine the organic layers and wash with water (300 mL), dry over Na2SO4, filter and concentrate to an oil. Dissolve the oil in acetonitrile and extract with hexane to remove the mineral oil to give 22.79 g N-methyl-N-(4-fluorobenzyl)acetamide: mp=48-54° C.; Rf=0.45 (4% MeOH/methylene chloride); 1H NMR (CDCl3) 7.27-6.93 (m, 4), 4.5 (d, 2), 2.91 (s, 3), 2.14 (s, 3).

Workup

  1. extractionextract with ethyl acetate (400 mL and 200 mL)
  2. washCombine the organic layers and wash with water (300 mL)
  3. dry with materialdry over Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate to an oil
  6. dissolutionDissolve the oil in acetonitrile
  7. extractionextract with hexane
  8. customto remove the mineral oil

Sources & evidence

ORD record
ord-9d2cdaed4ba040a1ba0d3aa01787c623
Source dataset
uspto-grants-2008_02
Patent number
US07326731B2

Reaction notes

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