Hydrochloric Acid → 6-chloro-5-fluoro-1H-pyrrolo[2,3-b]pyridine

Temperature

5 °C

To a stirred solution of 5-fluoro-1H-pyrrolo[2,3-b]pyridine 7-oxide (4.317 g, 28.38 mmol) in THF (150 mL) is added hexamethyldisilazane (6.54 mL, 31.22 mmol). The reaction mixture is cooled to 5° C. and methyl chloroformate (5.49 mL, 70.94 mmol) added dropwise. After stirring at 5° C. for 3 h, 2M sodium hydroxide (80 mL, 0.16 mol) is added dropwise, keeping temperature below 10° C. After 2 h, 2M hydrochloric acid solution is added until the mixture is at pH7. The reaction is poured onto brine (ca. 500 mL) and product extracted with CHCl3 (ca. 4×300 mL). The combined organic extracts are dried over magnesium sulphate, filtered, and concentrated in vacuo to give the title compound as a light brown solid (4.15 g, 24.33 mmol). MS (m/z): 171/173 (M+1). The following compounds are prepared essentially by the method of Preparation 31.

1. customtemperature below 10° C
2. waitAfter 2 h
3. additionThe reaction is poured onto brine (ca. 500 mL) and product
4. extractionextracted with CHCl3 (ca. 4×300 mL)
5. dry with materialThe combined organic extracts are dried over magnesium sulphate
6. filtrationfiltered
7. concentrationconcentrated in vacuo

ORD record

ord-0840e06025214a209b6c6e0f775ba3eb

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08778946B2