Reaction Steps
Preparation of 5-Chloro-2-methyl-4-thiocyanato-phenol (compound 20A) The title compound was prepared in a manner analogous to Example 1B from 5-chloro-2-methyl-phenol. 400 MHz 1H NMR (DMSO-d6) δ 10.60 (s, 1H), 7.54 (s, 1H), 6.98 (s, 1H), 2.07 (s, 3H). Step 2. Preparation of (5-Chloro-2-methyl-4-thiocyanato-phenoxy)-acetic acid methyl ester(compound 20B) The title compound was prepared from the product of Example 20A in a manner analogous to Example 1C. 400 MHz 1H NMR (DMSO-d6) δ 7.62 (s, 1H), 7.40 (s, 1H), 4.94 (s, 2H), 3.65 (s, 3H), 2.15 (s, 3H). Step 3. Preparation of (5-Chloro-4-mercapto-2-methyl-phenoxy)-acetic acid methyl ester (compound 20C) The title compound was prepared from (5-chloro-2-methyl-4-thiocyanato-phenoxy)-acetic acid methyl ester in a manner analogous to Example 1D. 400 MHz 1H NMR (DMSO-d6) δ 7.27 (s, 1H), 6.97 (s, 1H), 5.31 (s, 1H), 4.79 (s, 2H), 3.64 (s, 3H), 2.07 (s, 3H). Step 4. Preparation of [5-Chloro-2-methyl-4-(4′-trifluoromethyl-biphenyl-4-ylmethylsulfanyl)phenoxy]-acetic acid methyl ester (compound 20D) The title compound was prepared in the manner analogous to Example 1F using 3B and 20C. 400 MHz 1H NMR (DMSO-d6) δ 7.82 (d, 2H, J=8.3 Hz), 7.74 (d, 2H, J=8.3 Hz), 7.62 (d, 2H, J=8.3 Hz), 7.39 (d, 2H, J=8.3 Hz), 7.27 (s, 1H), 7.00 (s, 1H), 4.82 (s, 2H), 4.20 (s, 2H), 3.64 (s, 3H), 2.09 (s, 3H); MS m/z 480 (M+). Step 5. Preparation of [5-Chloro-2-methyl-4-(4′-trifluoromethyl-biphenyl-4-ylmethylsulfanyl)-phenoxy]-acetic acid (compound 20) The title compound was prepared in the manner analogous to Example 1 using 20D. mp 161-162° C.; 400 MHz 1H NMR (DMSO-d6) δ 7.83 (d, 2H, J=8.3 Hz), 7.74 (d, 2H, J=8.3 Hz), 7.62 (d, 2H, J=8.3 Hz), 7.51 (d, 2H, J=8.3 Hz), 7.26 (s, 1H), 6.95 (s, 1H), 4.69 (s, 2H), 4.20 (s, 2H), 2.08 (s, 3H); MS m/z 467 (M+1).
