Hydrochloric Acid → Methyl(4-fluoro-6-hydroxy-1-benzothiophen-3-yl)acetate

Temperatur

0 °C

To a suspension of aluminum chloride (713 mg) in toluene (10 mL) was added dodecane-1-thiol (4.00 mL) at 0° C. After stirring at 0° C. for 30 min, a solution of methyl(4-fluoro-6-methoxy-1-benzothiophen-3-yl)acetate (850 mg) in toluene (10 mL) was added dropwise to the mixture. The mixture was stirred at room temperature for 45 h. To the mixture was added aluminum chloride (713 mg) again, and the mixture was stirred at room temperature for 4 h. The mixture was poured into ice water. To the mixture was added 6N HCl, and the mixture was extracted with EtOAc. The EtOAc extract was washed successively with 1N HCl and brine, dried over MgSO4, and concentrated in vacuo. A mixture of the residue, conc. H2SO4 (0.5 mL) and MeOH (50 mL) was stirred at 75° C. for 4 h then concentrated in vacuo. To the residue was added saturated aqueous NaHCO3 and the mixture was extracted with EtOAc. The EtOAc extract was washed with brine, dried over MgSO4, and concentrated in vacuo. The residual crystals were washed with toluene and IPE to give the title compound (330 mg). The mother liquid was concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/hexane) to give the title compound (180 mg). Total yield, 510 mg. The crystals were recrystallized from acetone-hexane.

1. stirringThe mixture was stirred at room temperature for 45 h
2. stirringthe mixture was stirred at room temperature for 4 h
3. extractionthe mixture was extracted with EtOAc
4. extractionThe EtOAc extract
5. washwas washed successively with 1N HCl and brine
6. dry with materialdried over MgSO4
7. concentrationconcentrated in vacuo
8. additionA mixture of the residue, conc. H2SO4 (0.5 mL) and MeOH (50 mL)
9. stirringwas stirred at 75° C. for 4 h
10. concentrationthen concentrated in vacuo
11. additionTo the residue was added saturated aqueous NaHCO3
12. extractionthe mixture was extracted with EtOAc
13. extractionThe EtOAc extract
14. washwas washed with brine
15. dry with materialdried over MgSO4
16. concentrationconcentrated in vacuo
17. washThe residual crystals were washed with toluene and IPE

ORD-Eintrag

ord-3e204354a6734c5fba961fd0b9bb17e8

Quelldatensatz

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09238639B2