Triethylamine → 2-(2-Ethynylphenyl)acetamide

Participants

Reaction Steps

To a nitrogen de-gassed solution of 2-(2-iodophenyl)acetamide (I38) (1.75 g, 6.70 mmol) in dry THF (50 mL) and dry DMF (10 mL) was added Pd(PPh3)4 (0.194 g, 0.168 mmol) and Cu(I)I (0.064 g, 0.34 mmol), triethylamine (3.27 mL, 23.5 mmol). The mixture was stirred for 10 minutes and TMS-acetylene (1.52 mL, 10.7 mmol) was added. The reaction mixture was then stirred at room temperature for 18 hours, concentrated in vacuo and purified by silica gel chromatography (Biotage Isolera, 40 g Si cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) to give a beige solid. This material was dissolved in dry THF (25 mL) under an atmosphere of nitrogen and TBAF (1.0 M in THF, 2.805 mL, 2.805 mmol) was added dropwise at 0° C. The solution was stirred at this temperature for 1 hour and 15 minutes after which water (5 mL) was added. The reaction mixture was concentrated in vacuo and diluted with EtOAc (100 mL) and sat. aq. NaHCO3 (100 mL). The layers were separated and aqueous layer was extracted with EtOAc (100 mL), the organic layers were combined and washed with water (100 mL), brine (100 mL), dried (MgSO4), filtered and concentrated in vacuo to give the crude product. The material was purified by silica gel chromatography (Biotage Isolera, 40 g Si cartridge, 0-100% EtOAc in petroleum benzine 40-60° C., then 0-20% methanol in EtOAc) to give the title compound (I39) (0.239 g, 22% yield over 2 steps) as a beige solid; 1H NMR (400 MHz, d6-DMSO) δ 7.21 (dd, J=7.6, 1.1 Hz, 1H), 7.18-7.05 (m, 3H), 7.04-6.98 (m, 1H), 6.70 (s, 1H), 4.08 (s, 1H), 3.36 (s, 2H). LCMS Method C: rt 4.71 min; m/z 160.2 [M+H]+.

Provenance & Evidence