1,1-Dichloroethane → 8-(Benzyloxy)-N-(4-((3-methyloxetan-3-YL)methoxy)-2-nitrophenyl)quinolin-2-amine

Participants

Reaction Conditions

Reaction Steps

The compound, 8-Benzyloxy-quinolin-2-ol (5 g, 18.5 m,mol, 1.0 equivalent), 4-(3-Methyl-oxetan-3-ylmethoxy)-2-nitro-phenylamine (5.3 g, 22.2 mmol, 1.2 equivalents), cesium carbonate (8.46 g, 26 mmol, 1.4 equivalents), DIPHOS (1,2-Bis(diphenylphosphino)ethane; 443 mg, 111 μmol, 0.06 equivalents) and toluene (75 mL, 15 volumes) were charged to a 100 mL round bottom flask. The reaction was deoxygenated. Palladium acetate (83 mg, 37 μmol, 0.02 equivalents) was added and the reaction was deoxygenated again. The reaction was heated to 100° C. for 24–30 hours. At reaction completion, the reaction was cooled to 55° C. and dichloroethane (“DCE”; 75 mL, 15 volumes) was charged. The slurry was filtered through a pad of Celite and then the flask and filter were rinsed once with additional DCE.(50 mL, 10 volumes). The organics were concentrated to low volume and ethyl acetate (50 mL, 10 volumes) was added. The reaction was heated to reflux and allowed to cool to 20–25° C. The solids were granulated for 10–20 hours, filtered, and dried under vacuum at 40° C. with a slight nitrogen bleed to yield 6.72 g (8-Benzyloxy-quinolin-2-yl)-[4-(3-methyl-oxetan-3-ylmethoxy)-2-nitro-phenyl]-amine as an orange solid (77% yield). The material was judged to be about 95% pure by NMR, with ˜5% of the DIPHOS bis-oxide.

Provenance & Evidence