Reaktion #719804

Reaktionsgleichung

NBS

Na2S2O3

7-fluoro-6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene

5,7-difluoro-6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene

→

3-bromo-7-fluoro-6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene

Ausbeute 43.6%

3-bromo-5,7-difluoro-6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene

Ausbeute 24.6%

Lösungsmittel

DCM

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthen warmed to room temperature
2. 2
   workup.STIRRINGstirred for an additional 2 h
3. 3
   EinengenThe reaction mixture was concentrated
4. 4
   Sonstigeto afford the crude product
5. 5
   SonstigeThe organic layer was collected (phase separator)
6. 6
   Einengenconcentrated
7. 7
   workup.ADDITIONThe reaction mixture was diluted with water and DCM
8. 8
   SonstigeThe organic phase was collected (phase separator)
9. 9
   Einengenconcentrated
10. 10
    Sonstigeto afford the crude product
11. 11
    SonstigeThe crude material was purified by column chromatography (SiO2, 0-5% Heptanes/EtOAc)

Vorschrift

To a round bottom flask, an unseparated mixture of 7-fluoro-6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene and 5,7-difluoro-6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene (380 mg, 1.318 mmol) was dissolved in THF (10 mL) and the solution was cooled to 0° C. To the solution was added NBS (237 mg, 1.331 mmol). The reaction mixture was stirred at 0° C. for 1 h then warmed to room temperature and stirred for an additional 2 h. The reaction mixture was concentrated to afford the crude product. The crude product was diluted with DCM and set. Na2S2O3 (sodium thiosulfate). The organic layer was collected (phase separator) and concentrated. The reaction mixture was diluted with water and DCM. The organic phase was collected (phase separator) and concentrated to afford the crude product. The crude material was purified by column chromatography (SiO2, 0-5% Heptanes/EtOAc) to afford 3-bromo-7-fluoro-6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene (211 mg, 0.575 mmol 43.6% yield) and 3-bromo-5,7-difluoro-6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene (125 mg, 0.324 mmol, 24.62% yield). 3-bromo-7-fluoro-6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene: 1H NMR (400 MHz, CDCl3) δ ppm=7.56-7.66 (m, 2H), 7.46 (dd, J=1.01, 8.59 Hz, 1H), 7.11 (dd, J=7.58, 8.59 Hz, 1H), 6.90-6.97 (m, 2H), 3.92 (s, 3H), 3.79 (s, 3H), 3-bromo-5,7-difluoro-6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene: 1H NMR (400 MHz, CDCl3) δ ppm=7.53-7.68 (m, 2H), 7.48 (d, J=8.59 Hz, 1H), 7.15-7.27 (m, 1H), 7.07 (dt, J=2.53, 8.59 Hz, 1H), 3.98 (s, 3H), 4.02 (s, 3H).

Quelle