Dimethylformamide → 1H-Pyrrolo[2,3-b]pyridine-3-carbaldehyde

Temperature

-60 °C

To a suspension of 3-bromo-1H-pyrrolo[2,3-b]pyridine (9.85 g, 50.0 mmol) in THF (300 mL) was added dropwise a 2.5M solution of n-butyllithium in hexanes (42 mL, 105.0 mmol, 2.1 equiv.) at −70° C. The temperature of the reaction mixture was raised to −60° C. during the addition and became a clear solution. The resulting brick red color solution was slowly allowed to warm to −10° C. during a period of 1 h and then stirred for 4 h at this temperature. Again, the mixture was cooled to −70° C. and a solution of dimethylformamide (8.5 mL, 110.0 mmol) in THF (30 mL) was added dropwise. After addition, the mixture was allowed to warm to room temperature and stirred for 15 h. Then, the mixture was diluted with saturated ammonium chloride solution and the two layers were separated. The aqueous layer was extracted with ethyl acetate (2×150 mL). The combined organic extracts were washed with brine solution and dried over anhydrous magnesium sulfate. Filtration of the drying agent and removal of the solvent under the vacuum gave the crude brown solid which was dissolved in ethyl acetate (˜70 mL) at hot condition and then stored in the refrigerator overnight. The solids were collected by filtration and washed with ethyl acetate. After drying in air, 6.05 g (83% yield) of 1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde was isolated as an yellow solid: EI-HRMS m/e calcd for C8H6N2O (M+) 146.0480. found 146.0478.

1. temperatureto warm to −10° C. during a period of 1 h
2. temperatureAgain, the mixture was cooled to −70° C.
3. additionAfter addition
4. temperatureto warm to room temperature
5. stirringstirred for 15 h
6. customthe two layers were separated
7. extractionThe aqueous layer was extracted with ethyl acetate (2×150 mL)
8. washThe combined organic extracts were washed with brine solution
9. dry with materialdried over anhydrous magnesium sulfate
10. filtrationFiltration of the drying agent and removal of the solvent under the vacuum
11. customgave the crude brown solid which
12. customstored in the refrigerator overnight
13. filtrationThe solids were collected by filtration
14. washwashed with ethyl acetate
15. customAfter drying in air

ORD record

ord-f2acd3ca7bb244bab76509d1abc864a0

Source dataset

uspto-grants-2007_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07247727B2