Reaction Steps
Preparation of 3-Methoxy-4-thiocyanato-phenol (compound 21A) The title compound was prepared in a manner analogous to Example 1B from 3-methoxy-phenol. 400 MHz 1H NMR (DMSO-d6) δ 10.21 (s, 1H), 7.34 (d, 1H, J=8.3 Hz), 6.53 (s, 1H), 6.43 (d, 1H, J=8.3 Hz), 3.81 (s, 3H). Step 2. Preparation of (3-Methoxy-4-thiocyanato-phenoxy)-acetic acid methyl ester (compound 21B) The title compound was prepared from the product of Example 21A in a manner analogous to Example 1C. MS m/z 227 (M-CN). Step 4. Preparation of (4-Mercapto-3-methoxy-phenoxy)-acetic acid methyl ester (compound 21C) The title compound was prepared from (3-Methoxy-4-thiocyanato-phenoxy)-acetic acid methyl ester in a manner analogous to Example 1D. 400 MHz 1H NMR (DMSO-d6) δ 7.13 (d, 1H, J=8.5 Hz), 6.56 (s, 1H), 6.39 (d, 1H, J=8.5 Hz), 4.72 (s, 2H), 4.51 (s, 1H), 3.75 (s, 3H), 3.64 (s, 3H). Step 5. Preparation of [3-Methoxy-4-(4′-trifluoromethyl-biphenyl-4-ylmethylsulfanyl)-phenoxy]-acetic acid methyl ester (compound 21D) The title compound was prepared in the manner analogous to Example 1F using 3B and 21C. 400 MHz 1H NMR (DMSO-d6) δ 7.81 (d, 2H, J=8.3 Hz), 7.53 (d, 2H, J=8.3 Hz), 7.59 (d, 2H, J=8.3 Hz), 7.32 (d, 2H, J=8.3 Hz), 7.11 (d, 1H, J=8.5 Hz), 6.56 (s, 1H), 6.37 (d, 1H, J=8.5 Hz), 4.73 (s, 2H), 4.04 (s, 2H), 3.76 (s, 3H), 3.63 (s, 3H); MS m/z 463 (M+1). Step 6. Preparation of [3-Methoxy-4-(4′-trifluoromethyl-biphenyl-4-ylmethylsulfanyl)-phenoxy]-acetic acid (compound 21) The title compound was prepared in the manner analogous to Example 1 using 21D. 400 MHz 1H NMR (DMSO-d6) δ 7.83 (d, 2H, J=8.3 Hz), 7.76 (d, 2H, J=8.3 Hz), 7.61 (d, 2H, J=8.3 Hz), 7.34 (d, 2H, J=8.3 Hz), 7.13 (d, 1H, J=8.5 Hz), 6.56 (s, 1H), 6.39 (d, 1H, J=8.5 Hz), 4.63 (s, 2H), 4.06 (s, 2H), 3.77 (s, 3H); MS m/z 449 (M+1). Anal. Calc'd for C23H19F3O4S, C, 61.60; H, 4.27; found: C, 61.35; H, 4.25.
