Benzo(B)Thiophene → 1-Benzothiophene-2-carbaldehyde

Temperature

-15 °C

To a solution of thianaphthene (1.45 g, 10.5 mmol (97% pure)) in anhydrous Et2O (20 mL) at -15° C. was added dropwise a 1.6M solution of n-BuLi in hexane (9.9 mL, 15.7 mmol). The mixture was stirred at -15° C. (1.75 h) and at 25° C. (15 min). After recooling to -15° C., anhydrous N-methylformanilide (1.6 mL, 12.7 mmol) (distilled from CaH2) was added dropwise and the mixture was heated at reflux (30 min). The reaction mixture was quenched by addition of a mixture of 3N HCl (9 mL) and ice chips (20 mL). The organic phase was separated and the aqueous phase was extracted with Et2O (3×75 mL). The combined organic layers were washed with 1N HCl (3×40 mL), saturated aq. NaHCO3 (40 mL), dried (MgSO4), and evaporated to dryness. The residue was dissolved in EtOH (3 mL) and mixed with saturated aq. NaHSO3 (15 mL). The resulting mixture was allowed to stand for 30 min and the crystalline bisulfite addition product was collected by filtration, washing with Et2O (50 mL) and dried in a vacuum desicator. The yellow solid was dissolved in warm H2O (30 mL) and cooled to 0° C. Saturated aq. Na2CO3 was added and the mixture was stirred at 25° C. for 15 min. Filtration, washing with H2O and drying afforded benzo[b]thiophene-2-carboxaldehyde as an amorphous solid (1.25 g, 7.68 mmol) in 73% yield.

1. customat 25° C.
2. custom(15 min)
3. customAfter recooling to -15° C.
4. temperaturethe mixture was heated
5. temperatureat reflux (30 min)
6. customThe reaction mixture was quenched by addition of a mixture of 3N HCl (9 mL) and ice chips (20 mL)
7. customThe organic phase was separated
8. extractionthe aqueous phase was extracted with Et2O (3×75 mL)
9. washThe combined organic layers were washed with 1N HCl (3×40 mL), saturated aq. NaHCO3 (40 mL)
10. dry with materialdried (MgSO4)
11. customevaporated to dryness
12. dissolutionThe residue was dissolved in EtOH (3 mL)
13. additionmixed with saturated aq. NaHSO3 (15 mL)
14. waitto stand for 30 min
15. additionthe crystalline bisulfite addition product
16. filtrationwas collected by filtration
17. washwashing with Et2O (50 mL)
18. customdried in a vacuum desicator
19. dissolutionThe yellow solid was dissolved in warm H2O (30 mL)
20. temperaturecooled to 0° C
21. additionSaturated aq. Na2CO3 was added
22. stirringthe mixture was stirred at 25° C. for 15 min
23. filtrationFiltration
24. washwashing with H2O
25. customdrying

ORD record

ord-1a154f3da7d64e4ca082efffdc0e9293

Source dataset

uspto-grants-1992_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05128448