Diethyl 2-[bis(4-methoxybenzylsulfanyl)methylene]malonate → (E)-diethyl 2-(1-(4-methoxybenzylthio)-2-(4-bromopyridin-2-yl)but-1-enyl)malonate

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Reaction Conditions

Reaction Steps

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, 0° C. for 15 min, and then recooled to −78° C. A solution of 4-bromo-2-propylpyridine (2, 2.94 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, after which time a solution of diethyl 2-[bis(4-methoxybenzylsulfanyl)methylene]malonate (1, 7.03 g, 14.8 mmol) in tetrahydrofuran (40.0 mL) is 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 3 an orange oil. The product is purified by flash column chromatography (eluting with 5% ethyl acetate in methylene chloride.

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