Potassium Iodide → 5-fluoro-4-iodo-1H-indole

A solution of thallium tris(trifluoroacetate) (8.45 g, 15.6 mmol) in TFA (35 mL) was added to a solution of 5-fluoro-1H-indole-3-carboxylic acid methyl ester (2 g, 10.4 mmol) in TFA (10 mL) at room temperature and stirred for 2 h. The reaction mixture was evaporated in vacuo and the resulting residue suspended in water (25 mL) before being treated with a solution of potassium iodide (5.2 g, 31.3 mmol) in water (50 mL). The reaction mixture was treated with dichloromethane (100 mL) and methanol (5 mL) and the resulting precipitate removed by filtration through celite. The organic layer was separated, washed successively with sodium thiosulfate solution and brine, then dried (MgSO4) and evaporated in vacuo. The resultant material was dissolved in methanol (60 mL) and treated with 40% aqueous NaOH solution (60 mL) then refluxed for 2 h. The reaction mixture was cooled to RT and extracted with DCM/MeOH (ratio 95:5). The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The resultant residue was purified by column chromatography (silica gel, pentane:EtOAc 75:25) to provide 5-fluoro-4-iodo-1H-indole as a pale brown solid (1.05 g, 39%).

1. customThe reaction mixture was evaporated in vacuo
2. customthe resulting precipitate removed by filtration through celite
3. customThe organic layer was separated
4. washwashed successively with sodium thiosulfate solution and brine
5. dry with materialdried (MgSO4)
6. customevaporated in vacuo
7. dissolutionThe resultant material was dissolved in methanol (60 mL)
8. additiontreated with 40% aqueous NaOH solution (60 mL)
9. temperaturethen refluxed for 2 h
10. extractionextracted with DCM/MeOH (ratio 95:5)
11. dry with materialThe organic layer was dried (MgSO4)
12. filtrationfiltered
13. concentrationconcentrated in vacuo
14. customThe resultant residue was purified by column chromatography (silica gel, pentane:EtOAc 75:25)

ORD record

ord-2a08c217795448f8b4cdd6d9a5b37c54

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08168633B2