Water → Methyl 5-fluoro-1H-indole-3-carboxylate

A solution of 5-fluoroindole (5 g, 37.0 mmol) in DMF (40 mL) was treated at 0° C. with trifluoroacetic anhydride (6.1 mL, 42.6 mmol). After 30 min, the reaction was poured into water and the resulting precipitate collected by filtration, washed with water, then dried in vacuo. The solid was then dissolved in 10% aqueous NaOH (200 mL) and heated at reflux for 1 h. The reaction mixture was cooled to RT, washed with DCM and acidified with aqueous HCl. The resulting white precipitate was collected by filtration, washed with water, taken up in DCM, washed with water, dried (MgSO4) and evaporated in vacuo. The resulting material (5 g, 75%) was dissolved in methanol (80 mL) and treated with concentrated sulfuric acid (2 mL) then heated at reflux overnight. The reaction was cooled and the resulting precipitate collected, washed with water and concentrated in vacuo to give 5-fluoro-1H-indole-3-carboxylic acid methyl ester as a peach-coloured solid (4.5 g, 83%).

1. filtrationthe resulting precipitate collected by filtration
2. washwashed with water
3. customdried in vacuo
4. dissolutionThe solid was then dissolved in 10% aqueous NaOH (200 mL)
5. temperatureheated
6. temperatureat reflux for 1 h
7. washwashed with DCM
8. filtrationThe resulting white precipitate was collected by filtration
9. washwashed with water
10. washwashed with water
11. dry with materialdried (MgSO4)
12. customevaporated in vacuo
13. dissolutionThe resulting material (5 g, 75%) was dissolved in methanol (80 mL)
14. additiontreated with concentrated sulfuric acid (2 mL)
15. temperaturethen heated
16. temperatureat reflux overnight
17. temperatureThe reaction was cooled
18. customthe resulting precipitate collected
19. washwashed with water
20. concentrationconcentrated in vacuo

ORD record

ord-22fb1a281f074d92a5dfed537b31be09

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08168633B2