methyl 2-(2-phenylethynyl)benzoate

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 100 mL round-bottomed flask was added methyl 2-(phenylethynyl)benzoate 36 (157 mg, 0.665 mmol) in THF (1.33 mL) and MeOH (1.33 mL) and the solution was cooled to 0° C. Then, a 50% aqueous solution of hydroxylamine (2195 mg, 33.2 mmol) was added followed by a 4M aqueous solution of KOH (0.33 mL, 1.329 mmol) and the resulting colorless solution was stirred at 0° C. and allowed to slowly warm to rt for 20 h. The reaction mixture was partitioned between EtOAc and H2O. The aqueous layer was extracted with EtOAc (2×) and the combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The yellow oil was crystallized in Et2O and the filtrate was evaporated and triturated again in Et2O. The solids were combined to afford title compound 37 (67 mg, 43% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 10.98 (s, 1H), 9.20 (s, 1H), 7.61 (d, J=7.4 Hz, 1H), 7.55-7.43 (m, 814). LRMS (ESI): (calc.) 237.25 (found) 238.2 (MH)+ to slowly warm to rt for 20 h The reaction mixture was partitioned between EtOAc and H2O The aqueous layer was extracted with EtOAc (2×) the combined organic layers were washed with brine dried over MgSO4 filtered concentrated in vacuo The yellow oil was crystallized in Et2O the filtrate was evaporated triturated again in Et2O

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 2-bromobenzoate 34 (166 μL, 1.163 mmol) in acetonitrile (2906 μL) was added triethylamine (972 μL, 6.98 mmol) and phenylacetylene 35 (140 μl, 1.279 mmol). Then copper (I) iodide (11.07 mg, 0.058 mmol), and bis(triphenylphosphine)-palladium(II) chloride (20.40 mg, 0.029 mmol), were successively added, degassing between and after each addition of catalysts. The mixture was stirred at 75° C. overnight. The reaction mixture was partitioned between EtOAc and 1M HCl. The aqueous layer was extracted with fresh EtOAc and the combined organic layers were washed with water, brine, dried over MgSO4. The residue was purified via Biotage using EtOAc/Hex ((0:100 to 10:90); 25+S column), to afford compound 36 (157 mg, 57%). LRMS (ESI): (calc.) 236.08 (found) 237.2 (MH)+ degassing between and after each addition of catalysts The reaction mixture was partitioned between EtOAc and 1M HCl The aqueous layer was extracted with fresh EtOAc the combined organic layers were washed with water, brine dried over MgSO4 The residue was purified via Biotage