Hydrochloric Acid → (R)-(4-(benzyloxy)-2',6'-dimethyl-4'-((tetrahydrofuran-3-yl)oxy)biphenyl-3-yl)methanol

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Reaction Conditions

Reaction Steps

(R)-3-(4-Bromo-3,5-dimethylphenoxy)tetrahydrofuran 35a (731 mg, 2.69 mmol) was dissolved in 20 mL of dioxane, followed by addition of (2-(benzyloxy)-5-(4,4,5,5-tetramethyl-dioxaborolane-2-yl)phenyl)methanol (1.28 g, 3.76 mmol, prepared by a method disclosed in patent application US2011275797) and 4 mL of aqueous sodium bicarbonate solution (855 mg, 8.07 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (98 mg, 0.14 mmol). The reaction solution was heated to 70° C. and stirred for 4 hours. The resulting solution was cooled and poured into 100 mL of water, 1M hydrochloric acid was added dropwise to adjust the pH to 2-3, and extracted with ethyl acetate (30 mL×3). The combined organic extracts were washed with saturated sodium chloride solution (30 mL), dried with anhydrous magnesium sulphate, and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography with elution system B to obtain the title compound (R)-(4-(benzyloxy)-2′,6′-dimethyl-4′-((tetrahydrofuran-3-yl)oxy)biphenyl-3-yl)methanol 36a (637 mg, yield 63.7%) as a yellow oil.

Provenance & Evidence