Hexane → (4-Fluoro-3-isopropoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone

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A 3-liter four neck round-bottomed flask (flame dried) was charged 1-bromo-3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)benzene (72.88 g, 0.25 mol), 4-fluoro-3-isopropoxy-N-methoxy-N-methylbenzamide (60.39 g, 0.25 mol) and dry THF (700 mL) under N2. The solution was cooled to −76° C., and a solution of n-BuLi in hexane (2.5M, 100 mL, 0.25 mol) was drop-wise maintaining the reaction mixture temperature below −70° C. over a period of 40 min. The reaction mixture was stirred at −76° C. for 1.5 h then quenched with 1N HCl (500 mL). The mixture was concentrated in vacuo to half the volume and was partitioned between EtOAc and H2O (v/v 1:0.3, 1 L). The organic phase was separated and the aqueous layer was extracted with EtOAc (500 mL). The combined organic extracts were washed with brine and then concentrated in vacuo to give a yellow oil which was purified by column chromatography using CH2Cl2 in hexanes (0% to 20%) to give (4-fluoro-3-isopropoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone as a colorless oil contaminated with a by-product (49.0 g, 50%). LC-MS (10-90% MeOH in H2O with 0.1% TFA in a 2-min gradient) 393.2 (M+H), retention time=2.15 min.

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