Benzyl mercaptan → 7-(Benzylthio)-4-(2-methoxy-4-(trifluoromethyl)phenyl)-3-nitroquinoline

Participants

Reaction Conditions

Reaction Steps

A round-bottom flask was charged with 7-bromo-4-chloro-3-nitroquinoline (1.083 g, 3.77 mmol, from Capot Chemical, Zhejiang, China), (2-methoxy-4-(trifluoromethyl)phenyl)boronic acid (0.911 g, 4.14 mmol), potassium carbonate (1.562 g, 11.30 mmol), and PdCl2(dppf) (0.138 g, 0.188 mmol). The flask was flushed with Ar (g), then 1,4-dioxane (9.42 ml) and water (3.14 ml) were added. The flask was fitted with a reflux condenser and lowered into a 60° C. oil bath for 45 min. The mixture was diluted with water and extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was taken up in 1,4-dioxane (9.42 ml). Xantphos (0.109 g, 0.188 mmol), Pd2(dba)3 (0.086 g, 0.094 mmol), n,n-diisopropylethylamine (1.316 ml, 7.53 mmol), and benzyl mercaptan (0.490 ml, 4.14 mmol) were added in sequence. The reflux condenser was attached, and the flask was heated to 60° C. for 2 h. The mixture was cooled to room temperature, diluted with EtOAc, then filtered through diatomaceous earth. The filtrate was concentrated, and the residue was purified by chromatography on silica gel (40-g column, 25-g silica gel loading column, 0 to 40% EtOAc/Heptane) to give 7-(benzylthio)-4-(2-methoxy-4-(trifluoromethyl)phenyl)-3-nitroquinoline (1.4698 g, 3.12 mmol, 83% yield) as a yellow solid. NMR indicated a 70:30 mixture of desired product to bis-coupling byproduct form the first step. m/z (ESI) 471.2 (M+H)+.

Provenance & Evidence