Chloromethyl Methyl Ether → 3-methoxymethoxy-N-(1-methyl-1-phenylethyl)benzamide

HRID 21083

Reaction equation

HRID 21083 reaction equation
[C:1]([O:4][C:5]1[CH:6]=[C:7]([CH:20]=[CH:21][CH:22]=1)[C:8]([NH:10][C:11]([CH3:19])([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH3:12])=[O:9])(=[O:3])C.[OH-].[Na+].O.Cl.[CH:27](N(C(C)C)CC)(C)C.COCCl>CO.O>[CH3:27][O:3][CH2:1][O:4][C:5]1[CH:6]=[C:7]([CH:20]=[CH:21][CH:22]=1)[C:8]([NH:10][C:11]([CH3:19])([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH3:12])=[O:9]

Participants

8

Reactant 5

HCID 7864Chloromethyl Methyl Ether2×HCID 14798Sodium HydroxideHCID 81531Diisopropylethylamine2×HCID 21885828Hydrate;hydrochlorideHCID 684903353-acetoxy-N-(1-methyl-1-phenylethyl)benzamide

Product 1

HCID 684927953-methoxymethoxy-N-(1-methyl-1-phenylethyl)benzamideYield 84%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

3-Acetoxy-N-(1-methyl-1-phenylethyl)benzamide (9.57 g, 32.2 mmol) was dissolved in methanol (190 mL), and the solution was added with 4 mol/L sodium hydroxide solution (32.2 mL), followed by stirring at room temperature for 20 minutes. The reaction mixture was added with 1 mol/L hydrochloric acid water to adjust the pH to 7, and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in dichloromethane (190 mL), and the solution was added with diisopropylethylamine (16.8 mL, 96.6 mmol) and chloromethyl methyl ether (3.70 mL, 48.3 mmol) under ice-cooling. Then, the reaction mixture was warmed to room temperature and stirred for 2 hours. The mixture was added with diisopropylethylamine (5.60 mL, 32.2 mmol) and chloromethyl methyl ether (1.20 mL, 15.8 mmol), followed by further stirring for 2 hours. The reaction mixture was added with water and extracted with chloroform. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (chloroform/methanol=100/0, 99/1) to obtain 3-methoxymethoxy-N-(1-methyl-1-phenylethyl)benzamide (8.09 g, yield 84%).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. dissolutionThe residue was dissolved in dichloromethane (190 mL)
  6. temperaturecooling
  7. temperatureThen, the reaction mixture was warmed to room temperature
  8. stirringstirred for 2 hours
  9. stirringby further stirring for 2 hours
  10. extractionextracted with chloroform
  11. washThe organic layer was washed with saturated brine
  12. dry with materialdried over anhydrous sodium sulfate
  13. customThe solvent was evaporated under reduced pressure
  14. customThe residue was purified by flash column chromatography (chloroform/methanol=100/0, 99/1)

Sources & evidence

ORD record
ord-ba349968fa0843f6b91c6590150476ff
Source dataset
uspto-grants-2010_06
Patent number
US07745641B2

Linked notes

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