Hydrochloric Acid → 2-Cyclopropyl-1H-pyrrolo[2,3-B]pyridine

Temperature

0 °C

To a stirred mixture of N-boc-2-aminopicoline (10.4 g) in dry THF (70 ml) in an ice/salt bath was added, under an atmosphere of nitrogen, n-butyl lithium (2M solution in cyclohexane, 50 ml), keeping the temperature below 0° C. The reaction was stirred below 0° C. for 1 h before the addition of a solution of N-methyl-N-(methyloxy)cyclopropanecarboxamide (7.5 g) (available from Pfaltz-Bauer) in dry THF (20 ml). The reaction mixture was stirred at 0° C. for 2 h then warmed to 10° C. and poured into 5M hydrochloric acid (130 ml). The mixture was heated at 60° C. for 2 h, cooled and the aqueous layer separated. The aqueous layer was basified by the addition of 10M sodium hydroxide, with ice/water cooling, until the pH was 10-12. The resulting mixture was extracted with DCM (2×100 ml) and the combined organic extracts were washed with water (50 ml), dried using a hydrophobic frit and evaporated to give the title compound (7.89 g).

1. additionwas added, under an atmosphere of nitrogen
2. customthe temperature below 0° C
3. temperaturethen warmed to 10° C.
4. temperatureThe mixture was heated at 60° C. for 2 h
5. temperaturecooled
6. customthe aqueous layer separated
7. additionThe aqueous layer was basified by the addition of 10M sodium hydroxide, with ice/water cooling, until the pH was 10-12
8. extractionThe resulting mixture was extracted with DCM (2×100 ml)
9. washthe combined organic extracts were washed with water (50 ml)
10. customdried
11. customevaporated

ORD record

ord-9742a46b3ed247d6951293503f5175cc

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658635B2