Phenylacetic Acid → N-Methoxy-N-methyl-2-phenylacetamide

HRID 133799Notes

Reaction equation

HRID 133799 reaction equation
[C:1]1([CH2:7][C:8]([OH:10])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[CH3:12][NH:13][O:14][CH3:15].[OH-].[Na+]>O1CCCC1.O>[CH3:15][O:14][N:13]([CH3:12])[C:8](=[O:10])[CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 3

HCID 999Phenylacetic AcidHCID 14798Sodium Hydroxide2×HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)

Product 1

HCID 10419762N-Methoxy-N-methyl-2-phenylacetamideYield 100%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

Based on a procedure found in the literature (Guanti, G.; Banfi, L.; Riva, R. Tetrahedron 50(41), 1994, 11945-11966), a solution of phenylacetic acid (10 g, 73 mmol) in tetrahydrofuran (150 mL) is combined with a solution of N,O-dimethylhydroxylamine hydrochloride (13 g, 130 mmol) in water (150 mL). The pH is adjusted to 4.5 by the addition of 1 N aqueous sodium hydroxide solution. To the mixture is added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimine hydrochloride (36 g, 190 mmol) as a solution in water (510 mL) dropwise over 30 minutes. Over the course of the addition, pH is maintained at 4.5 by the addition of 1 N aqueous sodium hydroxide solution. The reaction mixture is allowed to stir for 3 hours at room temperature and is then saturated with sodium chloride and extracted thrice with ethyl acetate. The combined extracts are washed with saturated aqueous sodium hydrogen carbonate (×2), water, and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to yield a golden liquid (13 g, 100%). MS (ES+): (M+H)=180.1

Workup

  1. additionOver the course of the addition
  2. extractionsaturated with sodium chloride and extracted thrice with ethyl acetate
  3. washThe combined extracts are washed with saturated aqueous sodium hydrogen carbonate (×2), water, and saturated aqueous sodium chloride solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-7278071fc82c4637ac86a424ca315b41
Source dataset
uspto-grants-2008_06
Patent number
US07390910B2

Reaction notes

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