Water → methyl 2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate

Temperature

-78 °C

Lithium hexamethyldisilazide (3.6 mL, 3.6 mmol, 1M in THF) was added to a solution of 2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine (0.57 g, 3.04 mmol; see WO 2008/034860) in THF (20 mL) at −78° C. The reaction mixture was stirred at −78° C. for 5 minutes, then warmed up to 0° C. for 30 minutes, and finally warmed to room temperature for another 30 minutes. The mixture was cooled back to −78° C. where methyl chloroformate (0.35 mL, 4.55 mmol) was added dropwise. The mixture was slowly warmed up to room temperature and stirred for 16 hours. Water was then added, followed by dichloromethane. The layers were separated. The aqueous layer was extracted twice with dichloromethane. The organic layers were dried with sodium sulfate, filtered and concentrated in vacuo. The crude was purified by flash chromatography to afford methyl 2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (0.45 g, 61%).

1. temperaturewarmed up to 0° C. for 30 minutes
2. temperaturefinally warmed to room temperature for another 30 minutes
3. additionwas added dropwise
4. temperatureThe mixture was slowly warmed up to room temperature
5. stirringstirred for 16 hours
6. customThe layers were separated
7. extractionThe aqueous layer was extracted twice with dichloromethane
8. dry with materialThe organic layers were dried with sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe crude was purified by flash chromatography

ORD record

ord-d6b2e086dc8f4c3784d0cb805629ea09

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08338452B2