3-Trifluoromethyl-1H-pyrrolo[2,3-b]pyridine

Synthesis

General procedure for the synthesis of 3-(trifluoromethyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-3-ol from 3-(trifluoromethyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine: At 0 °C, 3-(trifluoromethyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-3-ol (1.2 g, 5.88 mmol) was dissolved in a tetrahydrofuran (15 mL) and pyridine (0.951 mL, 11.76 mmol) in a mixed solution and thionyl chloride (0.858 mL, 11.76 mmol) was added slowly. The reaction mixture was stirred at room temperature for 24 hours. Upon completion of the reaction, the mixture was poured into ice water and the pH was adjusted with saturated sodium carbonate solution to 6. Subsequently, the aqueous layer was extracted with dichloromethane, and the organic layers were combined and dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated to dryness. For complete removal of residual pyridine, toluene was added and concentrated to dryness, and this operation was repeated three times to give 3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine as a brown solid (1.13 g, 100% yield). The mass spectrum (ESI) showed m/z = 186.88 (MH+).

References

[1] Patent: US2011/280808, 2011, A1. Location in patent: Page/Page column 80
[2] Organic Process Research and Development, 2010, vol. 14, # 1, p. 168 - 173
[3] Synthesis, 2007, # 2, p. 251 - 258
[4] Patent: WO2014/111496, 2014, A1. Location in patent: Page/Page column 105
[5] Patent: WO2016/142310, 2016, A1. Location in patent: Page/Page column 72