Hydrochloric Acid → N-methyl-2-(2-phenoxyphenyl)-2-oxoacetamide

HRID 273926Notes

Reaction equation

HRID 273926 reaction equation
[CH:1]1[CH:6]=[CH:5][C:4]([O:7][C:8]2[C:13](Cl)=[CH:12][CH:11]=[CH:10][CH:9]=2)=[CH:3][CH:2]=1.[Mg].C(Br)C.[C:19](Cl)(=[O:23])[C:20](Cl)=[O:21].[CH3:25][NH2:26].Cl>C1COCC1>[CH3:25][NH:26][C:19](=[O:23])[C:20]([C:13]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[O:7][C:4]1[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=1)=[O:21]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 6329MethylamineHCID 6332Ethyl BromideHCID 65578Oxalyl chlorideHCID 759002-Chlorodiphenyl etherHCID 5462224Magnesium

Product 1

HCID 11780091N-methyl-2-(2-phenoxyphenyl)-2-oxoacetamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Procedure

In a stream of nitrogen gas, 2-chlorodiphenyl ether (10.23 g, 0.05 mol) in dry THF (20 ml) was dropwise added to a mixture of magnesium (1.34 g, 0.055 mol) and ethyl bromide (0.19 ml) in dry THF (15 ml) under reflux over 30 minutes. After further reflux for 6 hours, the reaction mixture was diluted with dry THF (15 ml) and cooled below 20° C. This mixture was dropwise added to oxalyl chloride (7.62 g, 0.06 mol) in dry THF (100 ml) at -10° to 0° C. over 15 minutes, followed by stirring at -10° to 0° C., and methylamine gas was introduced into the mixture, followed by stirring at room temperature for 15 minutes. After completion of the reaction, 1N HCl (100 ml) was added to the reaction mixture which was then extracted with toluene (300 ml). The extract was washed with water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/hexane to give N-methyl-2-(2-phenoxyphenyl)-2-oxoacetamide (8.07 g) as colorless crystals. The mother liquor was purified by silica gel chromatography (ethyl acetate/hexane) to give the objective compound (1.42 g). The total yield was 9.49 g (74%).

Workup

  1. temperatureunder reflux over 30 minutes
  2. temperatureAfter further reflux for 6 hours
  3. temperaturecooled below 20° C
  4. stirringby stirring at room temperature for 15 minutes
  5. additionwas added to the reaction mixture which
  6. extractionwas then extracted with toluene (300 ml)
  7. washThe extract was washed with water and brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-3f37b923392148bfb3d54cde9b96bf59
Source dataset
uspto-grants-1995_02
Patent number
US05387714

Reaction notes

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