Phosphoric Acid → 5-Bromo-1-benzothiophene

Temperature

130 °C

5-Bromobenzo[b]thiophene (Chemical Abstracts number 4923-87-9) was prepared as described in Banfield et al.; J. Chem. Soc.; 1956; 2603-2607, and in Seed, Alexander J.; et al. J. Mater. Chem.; vol10; 2000; 2069-2080. A mixture of phosphoric acid (218 g) and chlorobenzene (2 L) was heated at 130° C. and then treated with the product from Example 165A (107.0 g) over 2 hours using a syringe pump. The mixture was heated at 130° C. for 15 hours. Dean-Stark trap was used at the beginning of the reflux to remove water from the mixture. The mixture was allowed to cool to room temperature and quenched with 400 mL of water. The bottom aqueous layer was extracted with 200 mL of methylene chloride. The combined organic layer was washed with 200 mL of 10% Na2CO3, and concentrated to brown oil (129.4 g). The crude oil was dissolved in 1 L of 10:90 EtOAC:hexane, filtered through a short pad of silica gel and concentrated to a yellow oil (85.54 g, 95.8% yield). Further purification was done by column chromatography (silica gel, 5:95 EtOAc:hexane).

1. temperatureThe mixture was heated at 130° C. for 15 hours
2. temperaturereflux
3. customto remove water from the mixture
4. temperatureto cool to room temperature
5. customquenched with 400 mL of water
6. extractionThe bottom aqueous layer was extracted with 200 mL of methylene chloride
7. washThe combined organic layer was washed with 200 mL of 10% Na2CO3
8. concentrationconcentrated to brown oil (129.4 g)
9. dissolutionThe crude oil was dissolved in 1 L of 10:90 EtOAC
10. filtrationhexane, filtered through a short pad of silica gel

ORD record

ord-fca231b45cc04562b4f1a0fc8596efe3

Source dataset

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07538138B2