Reaction Steps
A solution of the product of step A (2.0 g, 3.79 mmol) in dichloromethane (15 mL) was cooled to 0° C. under a nitrogen atmosphere before addition of triethylsilane (5.0 mL, 31.38 mmol), TFA (4.4 mL, 55.74 mmol) and borontrifluoride-diethyletherate complex (7.0 mL, 55.74 mmol). The reaction mixture was stirred for 48 h at ambient temperature, then poured into K2CO3 (aq.) solution and extracted with dichloromethane. The combined organic layer was dried over Na2SO4, concentrated and the residue purified by flash column chromatography (SiO2, 98:2 hexanes/ethyl acetate) to give 3-(3-iodophenyl)tetrahydrofuran (0.89 g, 86%) as a colorless liquid: 1H NMR (CDCl3, 300 MHz) δ 7.60 (t, J=1.8 Hz, 1H), 7.56 (td, J=7.8 Hz, 1H), 7.22 (d, J=7.8 Hz, 1H), 7.04 (t, J=7.8 Hz, 1H), 4.15-4.00 (m, 2H), 3.96-3.84 (m, 1H), 3.76-3.66 (m, 1H), 3.33 (p, J=7.8 Hz, 1H), 2.43-2.29 (m, 1H), 2.04-1.89 (m, 1H). Step C: The product of step B was coupled with lithium 2-(tert-butoxycarbonyl)-6-chloro-1,2,3,4-tetrahydrobenzofuro[3,2-c]pyridine-8-sulfinate following the procedure of Example 50, step A. The crude product was purified by flash column chromatography (SiO2, 4:1 hexanes/ethyl acetate) to give tert-butyl 6-chloro-8-(3-(tetrahydrofuran-3-yl)phenylsulfonyl)-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylate (55 mg, 8%) as an off-white solid: 1H NMR (CDCl3, 300 MHz) δ 8.02-7.91 (m, 1H), 7.87-7.76 (m, 3H), 7.51-7.44 (m, 2H), 4.57 (s, 2H), 4.18-4.02 (m, 2H), 3.97-3.78 (m, 3H), 3.77-3.67 (m, 1H), 3.46 (p, J=7.5 Hz, 1H), 2.98-2.84 (m, 2H), 2.49-2.34 (m, 1H), 2.06-1.89 (m, 1H), 1.50 (s, 9H); APCI MS m/z 418 [(M+H)—C5H9O2]+.
