Reaction Steps
Alternatively, a key intermediate for the preparation of Cp-4 was obtained by the following method. A solution of 1,3-dimethyl-4-keto-4,5,6,7-tetrahydrothionaphthene (3.78 g, 21 mmol) in dichloroethane was treated with 2,6-di-t-butyl-4-methyl pyridine (5.3 g, 26 mmol) at 0° C. under nitrogen atmosphere. After 15 min trifluoromethanesulfonic anhydride (4.11 mL, 24 mmol) was added dropwise to the reaction and stirred overnight at room temperature under nitrogen. The solvent was evaporated in vacuo and the residue was triturated with pentane. This eluant was filtered through silica gel to afford 1,3-dimethyl-6,7-dihydrobenzo[c]thiophen-4-yl trifluoromethanesulfonate as a clear oil (3 g, 46%). 1H NMR (CDCl3) δ2.28 (s, 3H), 2.42 (t, 2H), 2.50 (s, 3H), 2.58 (t, 2H), 5.81 (t, 1H). A solution of this material (1.6 g, 5.12 mmol) and dioxane (150 mL) was added to 4-(tributyltin)-1-trityl-1H-imidazole (3.7 g, 5.12 mmol, prepared as described by Stille, Org. Synth., 1989, 68, 116), LiCl (0.65 g, 15.4 mmol), (Ph3P)4Pd (0.107 g, 0.09 mmol), and 2,6-di-t-butyl-4-methylphenol (0.002 g, 0.009 mmol). The reaction was deoxygenated with Argon and refluxed overnight. A solution of 30% KF/ether (1:1) was added and stirred overnight at room temperature. The reaction mixture was filtered through a plug of silica, rinsed with ethyl acetate (300 mL), extracted sequentially with NaHCO3 (sat'd), H2O, brine, dried with MgSO4, filtered and the solvent evaporated in vacuo to yield an oily residue. Crystals were precipitated with methylene chloride/hexane (80:20) and collected by filtration to yield 4-(1,3-dimethyl-6,7-dihydrobenzo[c]thiophen-4-yl)-1-trityl-1H-imidazole (1.7 g, 70%). Alternatively, 4-(1,3-dimethyl-6,7-dihydrobenzo[c]thiophen-4-yl)-1-tritylimidazole can be prepared by treating a solution of 4-iodo-1-tritylimidazole (1.4 g, 3.2 mmol, prepared as described by Turner and Lindel, J. Org. Chem. 1991, 56, 5739-5740) and methylene chloride (500 mL) at 0° C. with ethyl magnesium bromide (1.5 mL, 4.5 mmol). The reaction was stirred 15 min and then warmed to room temperature for 15 min. Ultrapure ZnCl2 (871 mg, 6.4 mmol) was added to the reaction mixture and stirred for 40 min. A solution of 1,3-dimethyl-6,7-dihydrobenzo[c]thiophen-4-yl trifluoromethanesulfonate (1.4 g, 3.2 mmol) in THF (30 mL) was added to the reaction, followed by Pd(PPh3)4 (0.185 g, 0.16 mmol). The reaction was purged with Argon for 10 min and heated to reflux for 15 hrs. The reaction was washed with 1N HCl followed by Na2CO3 (sat'd). The organic layer was dried with Na2SO4, filtered and the solvent evaporated in vacuo to yield 4-(1,3-dimethyl-6,7-dihydrobenzo[c]thiophen-4-yl)-1-tritylimidazole (1.2 g, 80%). mp 205-207° C. 1H NMR (CDCl3) δ1.78 (s, 3H), 2.25 (s, 3H), 2.26 (t, 2H), 2.55 (t, 2H), 6.20 (t, 1H), 6.73 (s, 1H), 7.28 (m, 6H), 7.35 (m, 9H), 7.45 (s, 1H). Anal. calcd for C32H28N2S.0.5H2O: C, 79.80; H, 6.07; N, 5.82. Found: C, 79.42; H, 5.85; N, 5.62. MS m/e 473 (M+H), 243 (Tr), 165.
