Triethylamine → Methyl 5-chloro-2-[2-(trimethylsilyl)ethynyl]benzoate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of methyl 2-bromo-5-chlorobenzoate (14.8 g, 59 mmol) in triethylamine (124 ml, 890 mmol) was added copper iodide (339 mg, 1.8 mmol) and triphenylphosphine (778 mg, 3.0 mmol) at room temperature, under nitrogen. This mixture was purged with nitrogen before the addition of ethynyl(trimethyl)silane (12.5 ml, 89 mmol) and Pd(OAc)2 (266 mg, 1.2 mmol). The reaction mixture was stirred at 50° C. for 20 hours and concentrated in-vacuo. The residue was dissolved in deionized water (50 ml) and EtOAc (50 ml) and filtered through Celite. The filter cake was washed with EtOAc (50 ml) before the phases were separated and the aqueous layer was extracted with EtOAc (2×50 ml). The combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography (10 g Silica Isolute cartridge, 1-15% EtOAc:Heptanes) to give the title compound (16.2 g, 93%) as an orange solid. LC-MS 91%, m/z=267.4, 268.9; 1H NMR (500 MHz, Chloroform-d) δ ppm 7.90 (d, J=2.21 Hz, 1H) 7.52 (d, J=8.35 Hz, 1H) 7.42 (dd, J=8.28, 2.29 Hz, 1H) 3.93 (s, 3H) 0.28 (s, 9H).

Provenance & Evidence