반응 단계
Lithium diisopropylamide (LDA) is formed by dropwise addition of n-butyllithium (1.6 M in hexanes, 10.1 mL, 16.2 mmol) to a stirred solution of diisopropylamine (2.3 mL, 16.4 mmol) in tetrahydrofuran (25.0 mL) at −78° C. The resulting solution is stirred at −78° C. for 5 min, stirred at 0° C. for 15 min, and then re-cooled to −78° C. A solution of 4-chloro-2-propylpyridine (2, 2.29 g, 14.7 mmol) in tetrahydrofuran (25.0 mL) is added dropwise to this solution over a period of 30 min. The resulting deep red suspension is stirred at −78° C. for 1 h. A solution of diethyl 2-[bis(4-methoxybenzylsulfanyl)methylene]malonate (1, 7.03 g, 14.8 mmol) in tetrahydrofuran (40.0 mL) is then added dropwise over a period of 15 min. The resulting yellow solution is stirred at −78° C. for 1.5 h, −15° C. for 1.5 h, and room temperature for 30 min. to give a dark orange solution. The reaction mixture is quenched with a saturated aqueous solution of ammonium chloride (100 mL) and extracted with diethyl ether (2×100 mL). The combined organic extracts are dried over magnesium sulfate and evaporated under reduced pressure to give an orange oil. The product is purified by flash column chromatography (eluting with 5% ethyl acetate in methylene chloride; Rf0.50) to give 3 as an orange oil. 1H NMR (DMSO-d6): δ0.76 (t, J=7.5 Hz, 3H, CH2CH3), 1.17 (t, J=7.0 Hz, 6H, 2×CO2CH2CH3), 2.81 (q, J=7.5 Hz, 2H, CH2CH3), 3.74 (s, 3H, OCH3), 4.01 (s, 2H, SCH2), 4.10 (q, J=7.0 Hz, 4H, 2×CO2CH2CH3), 4.41 (s, 1H, CH(CO2CH2CH3)2), 6.90 (m, 2H, benzylic H-3/H-5), 7.28 (m, 2H, benzylic H-2/H-6), 7.44 (d, J=2.0 Hz, 1H, pyridyl H-3), 7.52 (dd, J=5.5 Hz, 2.0 Hz, 1H, pyridyl H-5), 8.56 (d, J=5.5 Hz, 1H, pyridyl H-6). 13C{1H} NMR (DMSO-d6): δ12.4 (CH2CH3), 13.9 (CH(CO2CH2CH3)2), 28.3 (CH2CH3), 39.5 (SCH2), 55.0 (OCH3), 58.5 (CH(CO2CH2CH3)2), 61.1 (CH(CO2CH2CH3)2), 113.9 (benzylic C-3/C-5), 122.9 (pyridyl C-5), 123.0 (pyridyl C-3), 125.7 (═C(SAr)(CH(CO2CH2CH3)2)), 129.3 (benzylic C-1), 130.2 (benzylic C-2/C-6), 143.4 (pyridyl C-4, C—Cl), 150.6 (pyridyl C-6), 153.3 (═C(CH2CH3)(pyridyl)), 158.4 (benzylic C-4, C—OCH3), 159.1 (pyridyl C-1), 167.2 (CH(CO2CH2CH3)2). LCMS m/z calcd for C24H28ClNO5S 477 ([M+]); found 478 ([M+H]+).
