Reaction Steps
3-nitro-4-[2-(trimethylsilyl)ethynyl]benzonitrile (61 b) was prepared from aryl bromide 60b as an off-white solid (1.61 g, 66%): mp 81-82° C. (toluene/hexane); 1H NMR δ 8.69 (d, J=1.6 Hz, 1H), 8.20 (dd, J=8.0 and 1.6 Hz, 1H), 7.94 (d, J=8.2 Hz, 1H), 0.27 (s, 9H); HPLC (Method B) tR 8.39 min (100 area % at 254 nm). Anal. (C12H12N2O2Si) C, H, N. 3-chloro-4[(2-(trimethylsilyl)ethynyl]benzonitrile (61c). A mixture of aryl bromide 60c, (3.96 g, 18.2 mmol), (trimethylsilyl)acetylene (1.80 g, 18.23 mmol), PPh3 (0.24 g, 0.91 mol), Pd (PPh3)4 (0.11 g, 0.09 mmol), and CuI (0.17 g, 0.91 mmol) in piperidine was stirred at 90° C. for 1 h. The reaction mixture was poured into water and extracted into EtOAc. Column chromatography [hexanes/EtOAc (40:1)] gave a white solid (3.24 g, 37%); mp 82-83° C.; 1H NMR δ 8.27 (d, J=1.9 Hz, 1H), 8.02 (d, J=8.4 Hz, 1H), 7.78 (dd, J=8.3 and 1.9 Hz, 1H), 0.27 (s, 9H); HPLC (Method B) tR 9.41 min (100 area % at 265 nm). Anal. (C12H12ClNSi) C, H, N, Cl. 4-chloro-3-[2-(trimethylsilyl)ethynyl]benzonitrile (61e) was prepared from aryl iodide 60f to give a white solid (3.11 g, 88%): mp 72-73° C. (hexanes); 1H NMR δ 8.12 (d, J=1.6 Hz, 1H), 7.90 (dd, J=8.2 and 1.6 Hz, 1H), 7.80 (d, J=8.2 Hz, 1H), 0.27 (s, 9H); HPLC (Method B) tR 9.35 min (100 area % at 254 nm). Anal. (C12H12ClNSi) C, H, N, Cl. 4-methoxy-3-[(trimethylsilyl)ethynyl]benzonitrile (61f) was prepared from aryl bromide 60g to give a white solid (8.67 g, 80%): mp 63-64° C. (hexanes; 1H NMR δ 7.87 (d, J=2.2 Hz, 1H), 7.86 (dd, J=9.7 and 2.2 Hz, 1H), 7.24 (d, J=9.7 Hz, 1H), 3.91 (s, 3H), 0.27 (s, 9H); HPLC (Method B) tR 8.31 min (98.12 area % at 254 nm). Anal. (C13H15NOSi) C, H, N. 3-Chloro-4-(3-hydroxy-3-methylbut-1-ynyl)benzonitrile (62b). 2-Methyl-3-butyn-2-ol (2.5 equiv) was added to a mixture of an aryl bromide 60c, K2CO3 (2.5 equiv), CuI (4 mol %), PPh3 (8 mol %), and 10% Pd/C (2 mol %) in DME and water. See Bleicher, L. S. et al., J. Org. Chem., 63, 1109-1118 (1998). The biphasic mixture was stirred at reflux under Ar overnight, and was then filtered (Celite) and partitioned between water and EtOAc. Column chromatography gave a white solid (4.25 g, 77%): mp 63-65° C. (hexane); 1H NMR δ 8.18 (d, J=1.5 Hz, 1H), 7.83 (dd, J=8.1 and 1.6 Hz, 1H), 7.69 (d, J=8.1 Hz, 1H), 5.68 (s, 1H), 1.50 (s, 6H); HPLC (Method B) tR 5.00 min (100 area % at 265 nm). Anal. (C12H10ClNO) C, H, N, Cl.
