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

Temperature

70 °C

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.

1. temperatureThe resulting solution was cooled
2. extractionextracted with ethyl acetate (30 mL×3)
3. washThe combined organic extracts were washed with saturated sodium chloride solution (30 mL)
4. dry with materialdried with anhydrous magnesium sulphate
5. filtrationfiltered
6. concentrationThe filtrate was concentrated under reduced pressure
7. customThe residue was purified by silica gel column chromatography with elution system B

ORD record

ord-e8fbf75847da465ba50571bd5e7af61d

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09139548B2