Water → 2-((S)-6-((2'-(hydroxymethyl)-6'-methyl-4'-(((R)-tetrahydrofuran-3-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acid

The crude methyl 2-((S)-6-((2′-(acetoxymethyl)-6′-methyl-4′-(((R)-tetrahydrofuran-3-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate 35e (189 mg, 0.36 mmol) was dissolved in 10 mL of a mixture of the solvents of methanol and tetrahydrofuran (V/V=1:4), followed by addition of 1M aqueous lithium hydroxide solution (4 mL, 4 mmol). The reaction solution was stirred for 3 hours. The resulting solution was added with 50 mL of water and 5 mL of 2M aqueous sodium hydroxide solution. The aqueous phase was washed with ethyl acetate (30 mL), then 1M hydrochloric acid was added dropwise to adjust the pH to 2-3, and extracted with ethyl acetate (20 mL×2). 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 and the residue was purified by TLC with elution system A to obtain the title compound 2-((S)-6-((2′-(hydroxymethyl)-6′-methyl-4′-(((R)-tetrahydrofuran-3-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acid 35 (15 mg, yield 8.6%) as a white solid.

1. washThe aqueous phase was washed with ethyl acetate (30 mL)
2. addition1M hydrochloric acid was added dropwise
3. extractionextracted with ethyl acetate (20 mL×2)
4. washThe combined organic extracts were washed with saturated sodium chloride solution (30 mL)
5. dry with materialdried with anhydrous magnesium sulphate
6. filtrationfiltered
7. concentrationThe filtrate was concentrated under reduced pressure
8. customthe residue was purified by TLC with elution system

ORD-Eintrag

ord-495cdb8303314d02ab382772a8600a4c

Quelldatensatz

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09139548B2