Hydrochloric Acid → (R)-(3'-(hydroxymethyl)-6-methyl-4-((tetrahydrofuran-3-yl)oxy)biphenyl-2-yl)methyl acetate

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Reaction Conditions

Reaction Steps

The crude (R)-2-bromo-3-methyl-5-((tetrahydrofuran-3-yl)oxy)benzyl acetate 35c (658 mg, 2 mmol) was dissolved in 50 mL of dioxane, followed by addition of 3-hydroxymethyl phenylboronic acid (608 mg, 4 mmol) and 6 mL of aqueous potassium carbonate solution (636 mg, 4 mmol), and then [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (74 mg, 0.10 mmol). The reaction solution was heated to 70° C. and stirred for 4 hours. The resulting solution was cooled, poured into 100 mL 1M aqueous hydrochloric acid solution, 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)-(3′-(hydroxymethyl)-6-methyl-4-((tetrahydrofuran-3-yl)oxy)biphenyl-2-yl)methyl acetate 35d (476 mg, yield 66.8%) as a yellow oil.

Provenance & Evidence