Quinoline → 4-Bromobenzo[b]thiophene

Temperature

105 °C

Copper powder (49.8 g) is added to a stirred mixture of 4-bromo-benzo[b]thiophene-2-carboxylic acid (995.5 g, 3.87 mol) and quinoline (1.99 L) and the resultant mixture is heated to and maintained at 15 to 195° C. for 5 h. The mixture is allowed to cool to room temperature and the reaction is quenched by the addition of a mixture of ice (5.81 Kg) and concentrated hydrochloric acid (2.48 L). TBME (9 L) is added and the mixture is stirred vigorously for 10 min and filtered. The clarified layers are separated and the aqueous layer is extracted with TBME (1.0 L). The combined extracts are washed with hydrochloric acid (1 M, 2×5.00 L) and water (4.0 L), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to afford the crude product (640 g) as a brown oil which solidifies on standing overnight. The residue is slurried in methanol (500 mL, 0.5 vol) at −10 to 0° C. for 1.5 h, the observed solid material is collected by filtration and pulled dry on the filter. The methanolic mother liquors are concentrated by rotary evaporation. The residue is combined with the isolated solid material, slurried in TBME (2.0 L) and the collected solids are washed with TBME (660 L). The combined liquors and washes are washed with hydrochloric acid (1 M, 660 mL), saturated aqueous sodium hydrogen carbonate. (2×1.0 L) and water (4.0 L), dried over magnesium sulfate, filtered and concentrated by rotary evaporation at 40° C. to afford the crude product. The residue is slurried in methanol (1.10 L) at −10 to 0° C. for 1 h. The observed solid is collected by filtration and dried under vacuum at 20° C. to afford 4-bromo-benzo[b]thiophene as an off-white solid (315 g, 37%). 1H NMR (CDCl3): δ 7.81 (d, 1H, J=8.0 Hz), 7.57-7.48 (m, 3H), 7.21 (t, 1H, J=7.7 Hz).

1. temperatureto cool to room temperature
2. customthe reaction is quenched by the addition of a mixture of ice (5.81 Kg) and concentrated hydrochloric acid (2.48 L)
3. additionTBME (9 L) is added
4. filtrationfiltered
5. customThe clarified layers are separated
6. extractionthe aqueous layer is extracted with TBME (1.0 L)
7. washThe combined extracts are washed with hydrochloric acid (1 M, 2×5.00 L) and water (4.0 L)
8. dry with materialdried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customto afford the crude product (640 g) as a brown oil which
12. waiton standing overnight
13. filtrationthe observed solid material is collected by filtration
14. custompulled dry on the filter
15. concentrationThe methanolic mother liquors are concentrated by rotary evaporation
16. washthe collected solids are washed with TBME (660 L)
17. washThe combined liquors and washes are washed with hydrochloric acid (1 M, 660 mL), saturated aqueous sodium hydrogen carbonate
18. dry with material(2×1.0 L) and water (4.0 L), dried over magnesium sulfate
19. filtrationfiltered
20. concentrationconcentrated by rotary evaporation at 40° C.
21. customto afford the crude product
22. filtrationThe observed solid is collected by filtration
23. customdried under vacuum at 20° C.

ORD record

ord-576c5ee4192c4e758d0a419bcdb33e60

Source dataset

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07863302B2