Hydrochloric Acid → 1H-Pyrrolo(2,3-b)pyridine

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Reaction Conditions

Reaction Steps

(3-Methyl-pyridin-2-yl)-carbamic acid tert-butyl ester (5 g, 24 mmol) was dissolved in tetrahydrofuran (96 mL) and cooled in an ice-salt bath to −15° C. Butyl lithium solution (1.6 M in hexanes, 30 mL, 48 mmol) was added drop wise over 30 min. After an additional 1 h, N,N-dimethylformamide (1.9 mL, 34.5 mmol) was added and the reaction mixture warmed to 25° C. over 16 h. The reaction mixture was added very slowly to approximately 150 mL of 6M HCl solution. The resulting mixture was warmed to 55° C. for 2 h, then cooled, the phases separated, and ethyl acetate was added to the aqueous layer. 6M sodium hydroxide solution was slowly added until the pH 6, then the layers were separated and the aqueous layer was extracted once more with ethyl acetate. The combined ethyl acetate extracts were washed with sodium chloride solution, dried (sodium sulfate), filtered, and concentrated in vacuo to give 1H-pyrrolo[2,3-b]pyridine (3.8 g, 134%) as a brown semisolid. This was used directly in the next step without further purification. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 10.86 (br. s., 1H) 8.28 (dd, J=4.9, 1.5 Hz, 1H) 7.98 (dd, J=7.7, 1.7 Hz, 1H) 7.36 (d, J=3.4 Hz, 1H) 7.10 (dd, J=7.9, 4.9 Hz, 1H) 6.51 (d, J=3.4 Hz, 1H); LCMS (EI/CI) m/z: 119 [M+H].

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