Hydrochloric Acid → 5-Fluoro-2,3-dihydrobenzofuran-6-ol

Temperatur

1500 °C

To a stirred solution of 5-fluoro-6-hydroxy-benzofuran-3-one (551 mg, 3.28 mmol) in ethanol (10 mL) was added hydrazine hydrate (3.75 mL, 76.93 mmol), and the reaction was heated to reflux for 30 minutes. The reaction was subsequently concentrated in vacuo. The residue was then dissolved in ethylene glycol (10 mL), and then treated with potassium hydroxide (551.64 mg, 9.83 mmol). The reaction was then heated to 1500° C. for 3 hours. The reaction was poured into 2M aq. HCl (100 mL), and extracted with EtOAc (100 mL). The organic phase was washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was suspended in DCM (50 mL), and the reaction was filtered. The filtrate was concentrated in vacuo and loaded onto a silica column (25 g, SNAP cartridge), which was eluted with EtOAc:isohexane 0% to 50%. Fractions containing desired product were combined and concentrated in vacuo to give 5-fluoro-2,3-dihydrobenzofuran-6-ol (D95) (190.4 mg, 1.2352 mmol, 37.7% yield) as a colourless oil which crystallised on standing;

1. temperaturethe reaction was heated
2. temperatureto reflux for 30 minutes
3. concentrationThe reaction was subsequently concentrated in vacuo
4. dissolutionThe residue was then dissolved in ethylene glycol (10 mL)
5. extractionextracted with EtOAc (100 mL)
6. washThe organic phase was washed with brine
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. filtrationthe reaction was filtered
11. concentrationThe filtrate was concentrated in vacuo
12. washwas eluted with EtOAc
13. additionFractions containing desired product
14. concentrationconcentrated in vacuo

ORD-Eintrag

ord-129aee8b5215485f9027530e643e5b9a

Quelldatensatz

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09376436B2