Hydrochloric Acid → (S)-methyl 2-(6-((4'-hydroxy-2',6'-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate

(S)-Methyl 2-(6-((4′-((tert-butyldimethylsilyl)oxy)-2′,6′-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate 3 g (1.28 g, 2.40 mmol) was dissolved in 50 mL of tetrahydrofuran, followed by addition of 10 mL of 6 M hydrochloric acid. The reaction solution was stirred at room temperature for 12 hours. The resulting solution was concentrated under reduced pressure and the residue was mixed with 100 mL of ethyl acetate. The organic phase was washed with water (20 mL×2) and saturated sodium chloride solution (20 mL) successively, dried with anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure. The residue was mixed with 60 mL of methanol and 1 mL of concentrated sulfuric acid. The resulting solution was heated to 70° C. and stirred for 1.5 hours. The solution was concentrated under reduced pressure, mixed with 100 mL of ethyl acetate, washed with water (20 mL×2), dried with anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by elution system B to obtain the title compound (S)-methyl 2-(6-((4′-hydroxy-2′,6′-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate 3 h (670 mg, yield 67.0%) as a colorless oil.

1. concentrationThe resulting solution was concentrated under reduced pressure
2. additionthe residue was mixed with 100 mL of ethyl acetate
3. washThe organic phase was washed with water (20 mL×2) and saturated sodium chloride solution (20 mL) successively
4. dry with materialdried with anhydrous sodium sulfate
5. filtrationfiltered
6. concentrationThe filtrate was concentrated under reduced pressure
7. additionThe residue was mixed with 60 mL of methanol and 1 mL of concentrated sulfuric acid
8. temperatureThe resulting solution was heated to 70° C.
9. stirringstirred for 1.5 hours
10. concentrationThe solution was concentrated under reduced pressure
11. additionmixed with 100 mL of ethyl acetate
12. washwashed with water (20 mL×2)
13. dry with materialdried with anhydrous sodium sulfate
14. filtrationfiltered
15. concentrationThe filtrate was concentrated under reduced pressure
16. customthe residue was purified by elution system B

ORD record

ord-b53ab372a3e64dec874a34a6f96b9509

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09139548B2