Trifluoroacetic acid → 2-Bromo-4-hydroxy-1-phenyl-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid ethyl ester

Temperature

-78 °C

5-bromo-2-[(tert-butoxycarbonyl-ethoxycarbonylmethyl-amino)-methyl]-1-phenyl-1H-pyrrole-3-carboxylic acid ethyl ester (390 mg, 0.767 mmol) was dissolved in tetrahydrofuran (5 mL) and then cooled with an acetone-dry ice bath. Potassium tert-butoxide in tetrahydrofuran (0.92 mL, 0.92 mmol, 1 M solution) was added; after addition, the reaction was stirred for 10 min at −78° C. The cold bath was removed and the reaction was stirred for another 30 min at room temperature (RT) before quenching with saturated ammonium chloride aqueous solution and extracting with ethyl acetate. The organic phase was subsequently washed with saturated sodium chloride aqueous solution, dried with anhydrous sodium sulfate, and filtered, concentrated to give an oil containing crude intermediate 2-bromo-4-oxo-1-phenyl-1,4,5,7-tetrahydro-pyrrolo[2,3-c]pyridine-5,6-dicarboxylic acid 6-tert-butyl ester 5-ethyl ester, which was then dissolved in dichloromethane (20 mL) at room temperature. Trifluoroacetic acid (5 mL) was added; the resulting reaction mixture was stirred overnight at room temperature before all solvents were removed. The residue was dissolved in dichloromethane and basified with triethylamine, then air was bubbled through the solution for 5 hours. The solvent was then removed, and the residue was purified with column to give the title compound. 1H NMR (200 MHz, CDCl3): δ (ppm)=11.52 (s, 1H), 8.06 (s, 1H), 7.65-7.28 (m, 5H), 7.02 (s, 1H), 4.52 (q, 2H, J=7.4 Hz), 1.48 (t, 3H, J=7.4 Hz).

1. temperaturecooled with an acetone-dry ice bath
2. additionafter addition
3. customThe cold bath was removed
4. stirringthe reaction was stirred for another 30 min at room temperature (RT)
5. custombefore quenching with saturated ammonium chloride aqueous solution
6. extractionextracting with ethyl acetate
7. washThe organic phase was subsequently washed with saturated sodium chloride aqueous solution
8. dry with materialdried with anhydrous sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customto give an oil
12. customthe resulting reaction mixture
13. stirringwas stirred overnight at room temperature before all solvents
14. customwere removed
15. dissolutionThe residue was dissolved in dichloromethane and basified with triethylamine
16. customair was bubbled through the solution for 5 hours
17. customThe solvent was then removed
18. customthe residue was purified with column

ORD record

ord-9a5180e456ad4d198917d37d2417a7d1

Source dataset

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07696223B2