2,3-Dichloro-5,6-dicyano-1,4-benzoquinone → 2-(2-(4-Fluoro-benzyl)-5-(5-chloro-2-(methylthio)pyrimidin-4-yl)thiophen-3-yl)ethanol

Participants

Reaction Conditions

Reaction Steps

n-Butyllithium (5.4 mL, 1.6 M in hexanes, 8.63 mmol) was added dropwise to a solution of 2-(2-(4-fluorobenzyl)thiophen-3-yl)ethanol (0.97 g, 4.11 mmol) in anhydrous tetrahydrofuran (15 mL) at −78° C. The resulting mixture was stirred at −78° C. for 1 h and then a solution of 5-chloro-2-(methylthio)pyrimidine (0.79 g, 4.93 mmol) in 1 mL of tetrahydrofuran was added slowly. The mixture was stirred at −78° C. for 1 h and then at −40° C. for 2 h. The reaction was quenched with a solution (1.1 mL) of acetic acid and methanol (1:1) at −40° C. and then a solution of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (0.1.1 g, 4.93 mmol) in tetrahydrofuran (1 mL) was added. After complete addition the reaction was stirred at −40° C. for 1 h, then warmed to rt. 10 mL of aqueous sodium hydroxide (2 M) and 50 mL of water were added and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine (80 mL), dried over anhydrous sodium sulfate and filtered. The solvent was evaporated in vacuo and the product purified by flash chromatography eluting with ethyl acetate/hexane (1:4) to afford the title compound (0.45 g, 28%). MS (M+H)+ 395/397.

Provenance & Evidence