Phosphoric Acid → Methyl 4-(4-chloro-2-fluoro-3-methoxyphenyl)-2-methylnicotinate

Participants

Reaction Conditions

Reaction Steps

A mixture of methyl 4-chloro-2-methylnicotinate (1.5 g, 8.08 mmol), 2-(4-chloro-2-fluoro-3-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.316 g, 8.08 mmol), phosphoric acid, potassium salt (3.43 g, 16.16 mmol) and PdCl2(dppf)-CH2Cl2 adduct (0.660 g, 0.808 mmol) in 1,4-dioxane (25 mL) and water (5 mL) was purged with nitrogen for 5 min. The reaction was then heated to 100° C. for 18 h. After cooling, the reaction was diluted with water (50 mL) and extracted with ethyl acetate (2×75 mL). The combined organic layers were washed with brine solution, dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography using 50% ethyl acetate in hexanes to yield methyl 4-(4-chloro-2-fluoro-3-methoxyphenyl)-2-methylnicotinate (1.2 g, 2.52 mmol, 31% yield) as pale brown oil. LC/MS (ESI) m/e 309.9 [(M+H)+, calcd for C15H14ClFNO3 310.1]; LC/MS retention time (method D): tR=0.84 min.

Provenance & Evidence