Cesium carbonate → (S)-(4-fluoro-2',6'-dimethyl-4'-((tetrahydrofuran-3-yl)oxy)biphenyl-3-yl)methanol

Temperatur

90 °C

The crude (R)-tetrahydrofuran-3-yl methanesulfonate 1b (83 mg, 0.50 mmol), 4′-fluoro-3′-(hydroxymethyl)-2,6-dimethylbiphenyl-4-ol 18c (110 mg, 0.45 mmol) and cesium carbonate (293 mg, 0.90 mmol) were dissolved in 2 mL of N,N-dimethylformamide. The reaction mixture was heated to 90° C. and stirred for 12 hours. The resulting mixture was concentrated under reduced pressure, mixed with 10 mL of water and extracted with ethyl acetate (10 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 to obtain the crude title compound (S)-(4-fluoro-2′,6′-dimethyl-4′-((tetrahydrofuran-3-yl)oxy)biphenyl-3-yl)methanol 18d (150 mg) as a colorless slime, which was directly used in the next step without further purification.

1. concentrationThe resulting mixture was concentrated under reduced pressure
2. additionmixed with 10 mL of water
3. extractionextracted with ethyl acetate (10 mL×3)
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

ORD-Eintrag

ord-e90bd396ebbc497892c5ca8270281145

Quelldatensatz

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09139548B2