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

Temperature

80 °C

To a solution of 5-fluoroindole (2.5 g, 18.5 mmol) in dioxane (75 mL) was added pyridine (14.9 mL, 185 mmol) and trichloroacetyl chloride (10.3 mL, 92.5 mmol). The resulting mixture was stirred at 80° C. for 2.5 hours, poured into ice water and extracted with ethyl acetate. The organic phase was washed with water, brine, dried and evaporated. The residue was dissolved in dry methanol (100 mL), sodium hydroxide (0.25 g) was added and the mixture heated at 80° C. for 30 min. Most of the solvent was evaporated and the residue was partitioned between water and ethyl acetate. The organic phase was washed with brine. dried and concentrated. Purification by silica gel chromatography (heptane-ethyl acetate, 3:1/1:1) gave 3.32 g (93%) of the sub-title compound.

1. extractionextracted with ethyl acetate
2. washThe organic phase was washed with water, brine
3. customdried
4. customevaporated
5. dissolutionThe residue was dissolved in dry methanol (100 mL)
6. additionsodium hydroxide (0.25 g) was added
7. temperaturethe mixture heated at 80° C. for 30 min
8. customMost of the solvent was evaporated
9. customthe residue was partitioned between water and ethyl acetate
10. washThe organic phase was washed with brine
11. customdried
12. concentrationconcentrated
13. customPurification by silica gel chromatography (heptane-ethyl acetate, 3:1/1:1)

ORD record

ord-66407ee1229d41d6a9b11e98ab1f8e2b

Source dataset

uspto-grants-2002_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06492406B1