Quinoline → 2-Chloro-3-nitro-5-(trifluoromethyl)pyridine

Participants

Reaction Steps

3-nitro-5-(trifluoromethyl)pyridin-2-ol (6.80 g, 32.7 mmol) and quinoline (2.72 g, 21.06 mmol) were combined in a 200 mL round-bottom flask with an oversized magnetic stir bar. The assembly was cooled with an RT water bath. Phosphorus oxychloride (4.07 ml, 43.7 mmol) was cautiously added with vigorous stirring. After 5 mm, the resulting gel would no longer stir. The apparatus was equipped with a reflux condenser and was transferred to a 120° C. oil bath. The gel quickly melted and stirring resumed with gentle refluxing. After 3 h, the mixture was cooled to RT and added portion wise to ice water with vigorous stirring. Sodium hydroxide was added to adjust the alkalinity to pH 8-9 and the mixture was extracted with EtOAc (2×100 mL) and CH2Cl2 (2×100 mL). The combined organics were dried (MgSO4), concentrated in vacuo and chromatographed (EtOAc/CH2Cl2) provided 2-chloro-3-nitro-5-(trifluoromethyl)pyridine (6.65 g, 90% yield) as a yellow liquid. 1H NMR (400 MHz, DMSO-d6): δ 9.21 (m, 1 H), 9.09 (m, 1 H).

Provenance & Evidence