Ammonium Chloride → 5-Chloro-3-hydroxy-3-(4-methoxy-pyridin-3-yl)-1,3-dihydro-indol-2-one

Temperature

-78 °C

A 1.7 M solution of tert-butyllithium in pentane (43.4 mL) was added to THF (150 ml) at −78° C. 2-Bromomesitylene (5.4 mL) was added dropwise, keeping the temperature below −60° C., and the mixture stirred at −78° C. for 1 h. 4-Methoxypyridine (2.75 mL) was added dropwise at −78° C. and then the mixture was stirred at −30° C. to −20° C. for 3.5 h. The reaction mixture was re-cooled to −78° C. and a slurry of 5-chloroisatin (2.44 g) in THF (120 ml) was added portionwise, keeping the temperature below −65° C. The reaction mixture was stirred at −78° C. for 30 min. The reaction mixture was allowed to warm to −20° C. and then 10% aqueous ammonium chloride solution (75 mL) was added. After stirring for 10 min, the white solid was filtered off, washed with water (excess) and ethyl acetate (20 mL). Yield after drying in vacuo: 1.8 g (42%).

1. customthe temperature below −60° C.
2. stirringthe mixture was stirred at −30° C. to −20° C. for 3.5 h
3. temperatureThe reaction mixture was re-cooled to −78° C.
4. customthe temperature below −65° C
5. stirringThe reaction mixture was stirred at −78° C. for 30 min
6. temperatureto warm to −20° C.
7. stirringAfter stirring for 10 min
8. filtrationthe white solid was filtered off
9. washwashed with water (excess) and ethyl acetate (20 mL)
10. customYield
11. customafter drying in vacuo

ORD record

ord-e7a311abdc564581a30b695c770bb71a

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08580842B2