4-(methoxymethoxy)phenol

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 60% sodium hydride (1.80 g, 45.0 mmol) and dry THF (20 mL) was cooled to −20° C. After addition of a solution of hydroquinone (2.00 g, 18.2 mmol) in THF (30 mL), the mixture was stirred at room temperature for one hour and then cooled again to −20° C. After dropwise addition of chloromethyl methyl ether (1.3 mL, 18.0 mmol), the cooled mixture was slowly warmed to 10° C., stirred at room temperature for one hour, and poured onto ice pieces (500 g). To the resulting mixture was added 3 mol/L aqueous hydrochloric acid until the mixture reached pH 4-5. Subsequently, the mixture was subjected to extraction with dichloromethane (100 mL×2). The extract was washed with water (100 mL×2) and saturated aqueous sodium chloride (100 mL), dried over anhydrous sodium sulfate, and placed under reduced pressure to distill the solvent off. The residue was purified by silica gel column chromatography (ethyl acetate/hexane), to obtain 581 mg (yield 21%) of the titled compound as pale yellow oil. cooled again to −20° C the cooled mixture was slowly warmed to 10° C. stirred at room temperature for one hour poured onto ice pieces (500 g) Subsequently, the mixture was subjected to extraction with dichloromethane (100 mL×2) The extract was washed with water (100 mL×2) and saturated aqueous sodium chloride (100 mL) dried over anhydrous sodium sulfate to distill the solvent off The residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2.91 g (9.3 mmol) of 2-bromo-N-(4-(trifluoromethoxy)phenyl)propanamide, 1.58 g (10 mmol) of 4-(methoxymethoxy)phenol, 1.52 g (11 mmol) of powdered, anhydrous potassium carbonate and 35 ml of acetonitrile was warmed, under N2, at reflux for a period of 5.5 hours and then stirred at room temperature overnight. The resulting mixture was poured into water and extracted with two portions of ether. The combined organic layers were washed twice with 5 percent aqueous NaOH, treated with charcoal and MgSO4, filtered and the filtrates evaporated to dryness. The residue was recrystallized from hexane to leave 1.77 g (49 percent of theoretical) of the above-named product as a colorless solid, m.p. 115°-116° C. The product is identified on the basis of IR and NMR analyses. at reflux for a period of 5.5 hours extracted with two portions of ether The combined organic layers were washed twice with 5 percent aqueous NaOH treated with charcoal and MgSO4 filtered the filtrates evaporated to dryness The residue was recrystallized from hexane