4-Aminophenol → 4-(2-Chloro-pyridin-4-yloxy)-phenylamine

Participants

Reaction Conditions

Reaction Steps

4-Amino-phenol (1.05g, 9.40 mmol, 1.1 equiv) is added in one portion to a suspension of NaH (60% free-flowing powder moistened with oil, 0.513 g, 12.8 mmol, 1.5 equiv) in dioxane abs. (6.5 mL), under an argon atmosphere. When hydrogen evolution subsides, a solution of 2-chloro-4-nitropyridine (1.35 g, 8.54 mmol) in dioxane (6 mL) is added. The resulting dark mixture is heated to 100° C. (oil bath temperature) for 70.5 h, allowed to cool to rt, quenched by addition of MeOH and partially concentrated in vacuo. The oily residue is dissolved in CH2Cl2/MeOH (80/20) and filtered through a glass sintered funnel containing silica gel (18 g), eluting with CH2Cl2/MeOH (90/10). The filtrate is partially concentrated in vacuo, diluted with CH2Cl2/MeOH (90/10) and purified by silica gel (70 g) column chromatography (CH2Cl2/Et2O, 90/10, then 85/15). A second column chromatography purification affords the title compound as a yellow solid: ES-MS: 221.1 [M+H]+; single peak at tR=6.56 min (System 2); Rf=0.27 (CH2Cl2/Et2O, 80/20).

Provenance & Evidence