Reaction Steps
A THF (2 mL) solution of 3-(fluoro)phenethyl alcohol (168 mg, 1.2 mmol) and DEAD (205 μL, 1.3 mmol) was very slowly added dropwise at 0° C. to a THF (4 mL) solution of triphenylphosphine (341 mg, 1.3 mmol) and 4-cyanophenol (119 mg, 1.0 mmol). The mixture was stirred at 0° C. (30 min), and then at room temperature (16 h). A saturated aqueous solution of NH4Cl (200 mL) was added dropwise at 0° C. The volatiles were evaporated under vacuum and the residue was purified by flash column chromatography on silica gel with EtOAc/hexanes (0/10 to 2/8) as the eluant to obtain 4-((3′-fluoro)phenethoxy)benzonitrile as a white solid (180 mg, 75%): Rf=0.33 (EtOAc/hexanes 1/9); mp 79-81° C.; IR (crystal) 3281, 2909, 2222, 1711, 1643, 1603, 1589, 1506, 1489, 1450, 1418, 1300, 1250, 1171, 1140, 1115, 1057, 1024, 941 cm−1; 1H NMR (400 MHz, CDCl3) δ 3.11 (t, J=7.0 Hz, CH2), 4.22 (t, J=7.0 Hz, OCH2), 6.92-7.06 (m, 5 ArH), 7.20-7.31 (m, 1 ArH), 7.57 (d, J=8.0 Hz, 2H3); 13C NMR (100 MHz, CDCl3) δ 35.2 (d, J=1.6 Hz, CH2), 68.5 (CH2O), 104.1 (C1), 113.6 (d, J=21.0 Hz, C2′ or C4′), 115.2 (C3), 115.9 (d, J=20.9 Hz, C4′ or C2′), 119.1 (CN), 124.6 (d, J=3.1 Hz, C6′), 130.0 (d, J=8.6 Hz, C5′), 134.0 (C2), 140.2 (d, J=7.0 Hz, C1′), 161.9 (C4), 162.9 (d, J=247.7 Hz, C3′); HRMS (M+H+) (ESI+) not observed [M+H+] (calcd for C13H8FNOH+ 214.0668); Anal. Calcd. for C15H12FNO: C, 74.67; H, 5.01; F, 7.87; N, 5.81. Found: C, 74.46; H, 5.11; F, 7.89; N, 5.83.
