Reacción #49361

Ecuación de reacción

diisopropylethylamine

chloromethyl methyl ether

hydrochloric acid water

sodium hydroxide

diisopropylethylamine

chloromethyl methyl ether

3-Acetoxy-N-(1-methyl-1-phenylethyl)benzamide

→

3-methoxymethoxy-N-(1-methyl-1-phenylethyl)benzamide

Rendimiento 84.0%

Disolventes

water

methanol

Condiciones de reacción

Tratamiento posterior

1. 1
   Extracciónextracted with ethyl acetate
2. 2
   LavadoThe organic layer was washed with saturated brine
3. 3
   Secadodried over anhydrous sodium sulfate
4. 4
   OtroThe solvent was evaporated under reduced pressure
5. 5
   workup.DISSOLUTIONThe residue was dissolved in dichloromethane (190 mL)
6. 6
   Temperaturacooling
7. 7
   TemperaturaThen, the reaction mixture was warmed to room temperature
8. 8
   workup.STIRRINGstirred for 2 hours
9. 9
   workup.STIRRINGby further stirring for 2 hours
10. 10
    Extracciónextracted with chloroform
11. 11
    LavadoThe organic layer was washed with saturated brine
12. 12
    Secadodried over anhydrous sodium sulfate
13. 13
    OtroThe solvent was evaporated under reduced pressure
14. 14
    OtroThe residue was purified by flash column chromatography (chloroform/methanol=100/0, 99/1)

Procedimiento

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%).

Fuente