[H-].[Na+].[C:3]1([OH:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl[C:11]1[C:20]2[N:21]=[CH:22][N:23]([CH2:24][CH2:25][O:26][CH2:27][C:28]#[CH:29])[C:19]=2[C:18]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N:12]=1.[O-]C1C=CC=CC=1.[Na+]>COCCOCCOC>[O:9]([C:11]1[C:20]2[N:21]=[CH:22][N:23]([CH2:24][CH2:25][O:26][CH2:27][C:28]#[CH:29])[C:19]=2[C:18]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N:12]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1A dried round bottom flask was charged with a stir bar, sodium hydride (8.15 g, 203.9 mmol) and anhydrous 2-methoxylethyl ether (diglyme, 100 mL) while under a nitrogen atmosphere and at ambient temperature. Phenol (20.7 g, 220.2 mmol) was added in several portions as a solid and the resulting solution stirred under a nitrogen atmosphere until gas evolution ceased. 4-chloro-1-[2-(prop-2-ynyloxy)ethyl]-1H-imidazo[4,5-c]quinoline (46.6 g, 163.1 mmol) was added neat and the solution was heated to 110° C. After 15.5 hours, a preformed solution of sodium phenoxide (phenol 5 g, 53.1 mmol and sodium hydride 1.91 g, 47.8 mmol) in diglyme (20 mL) was added to the reaction solution and heating was increased to 165° C. The reaction was judged complete after 1 hour at 165° C. After cooling to less than 70° C., the volatiles were removed under reduced pressure and the resulting brown solid was partitioned between chloroform and saturated aqueous sodium carbonate. The aqueous fraction was extracted with chloroform; the combined organic fractions were dried with anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure to provide a brown solid. The solid was recrystallized from acetonitrile with a small amount of dimethyl formamide to provide 25 g of 4-phenoxy-1-[2-(prop-2-ynyloxy)ethyl]-1H-imidazo[4,5-c]quinoline as a crystalline solid.
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