Reaction Steps
To a solution of 4-[4-(4-bromophenoxy)phenylsulfonylmethyl]-tetrahydropyran-4-carboxylic acid (1.10 g, 2.42 mmol) of in N,N-dimethylformamide (15 mL) was added tetrakis(triphenylphosphine)palladium(O) (108 mg), 2-thiophene boronic acid (857 mg, 6.70 mmol), followed by 2M aqueous sodium carbonate (2.7 mL, 5.4 mmol). The reaction was heated to reflux for 10 hours, cooled to room temperature, and the mixture partitioned between methylene chloride (100 mL) and 1N aqueous hydrochloric acid (20 mL). The aqueous layer was back extracted with methylene chloride (100 mL), and the combined organic layers dried (MgSO4), the residue chromatographed over 100 g of silica gel (eluted with methylene chloride to 10% methanol/methylene chloride), and the resulting foam crystallized from the minimum amount of methylene chloride/hexanes to afford 4-[4-(4-(thiophen-2-yl)phenoxy)phenylsulfonylmethyl]-tetrahydropyran-4-carboxylic acid (1.04 g, 94%). mp 181.2-193.3° C.; IR (KBr) 3432 (br), 1718.9 cm-1 ; 1H NMR (DMSO-d6) δ 1.67 (ddd, J=13.8, 9.4, 4.0 Hz, 2H), 1.95 (dm, J=13.8 Hz, 2H), 3.47 (mc, 2H), 3.67 (mc, 2H), 3.68 (s, 2H), 7.14 (dd, J=4.9, 3.6 Hz, 1H), 7.20 (d, J=8.8 Hz, 2H), 7.22 (d, J=8.9 Hz, 2H), 7.50 (dd, J=3.6, 1.2 Hz, 1H), 7.54 (dd, J=4.9, 1.2 Hz, 1H), 7.74 (d, J=8.8 Hz, 2H), 7.87 (d, J=8.8 Hz, 2H), 12.80 (s, 1H); 13CNMR (DMSO-d6) δ 32.92 (t), 42.25 (s), 61.73 (t), 63.26 (t), 117.82 (d), 123.75 (d), 125.66 (d), 127.39 (d), 128.50 (d), 130.08 (d), 130.74 (s), 134.90 (s), 142.42 (s), 154.13 (s), 161.33 (s), 174.39 (s); FABHRMS Calcd. for C23H24S2O6 (M+ +H): 459.0936. Found: 459.0936. Anal. Calcd. for C23H23S2O6 : C, 60.24; H, 4.83. Found: C, 60.57; H, 4.90.
