Trimethylsilylacetylene → HCID 12135110, compound

Participants

Reaction Steps

The product of Example 2, Step C, 2-(2-chloro-4-iodo-phenylamino)-3,4-difluoro-N-(2-hydroxy-ethoxy)-benzamide (3.25 g, 6.93 mmol) and (trimethylsilyl)acetylene (1.10 mL, 7.78 mmol) were combined in triethylamine (17 mL). Dichlorobis(triphenylphosphine)-palladium(II) (0.120 g, 0.017 mol) and cuprous iodide (0.033 g, 0.17 mmol) were added and the resultant solution was stirred at ambient temperature for 22 hours. The reaction mixture was adsorbed onto Celite® for 20 mm and was filtered, washing with ethyl acetate. The filtrate was concentrated to a thick oil, further diluted with ethyl acetate (100 mL) and washed with aqueous citric acid (2 M, 2×25 mL), water, and brine. The organic layer was then dried over magnesium sulfate and concentrated in vacuo to afford a tan-colored solid. Recrystallization from heptane-ethyl acetate afforded 2-(2-chloro-4-trimethylsilanylethynyl-phenylamino)-3,4-difluoro-N-(2-hydroxy-ethoxy)-benzamide (2.34 g, 76% yield) as a grey-colored solid: 1H NMR (400 MHz, DMSO-d6) δ 11.96 (s, 1 H), 8.95 (s, 1 H), 7.53 (d, J=1.7 Hz, 1 H), 7.47 (m, 1 H), 7.32 (m, 1 H), 7.27 (dd, J=8.4, 1.8 Hz, 1 H), 6.72 (dd, J=8.0, 6.6 Hz, 1 H), 4.73 (t, J=5.5 Hz, 1 H), 3.87 (apparent t, J=4.7 Hz, 2 H), 3.57 (m, 2 H), 0.21 (s, 9H); MS (APCI+)=439.1; MS (APCI−)=437.1.

Provenance & Evidence