Pentane → 5-Chloro-3-(2-methoxypyridin-3-yl)-3-hydroxy-1,3-dihydroindol-2-one

Temperature

-78 °C

A 1.7 M solution of tert-butyllithium in pentane (28.9 ml, 49.1 mmol) was added to THF (100 ml) at −78° C. 2-Bromomesitylene (3.6 ml, 23.4 mmol) was added dropwise and the mixture stirred at −78° C. for 1 h. 2-Methoxypyridine (1.92 ml, 18 mmol) was added at −78° C. and then the mixture was stirred at 0° C. for 1 h and at ambient temperature for 0.5 h. A suspension of 5-chloroisatin (1.27 g, 9.0 mmol) in THF (50 ml) was added dropwise at −78° C. The reaction mixture was allowed to warm to room temperature and then saturated ammonium chloride solution was added. The mixture was extracted three times with ethyl acetate, and the collected extracts were washed with saturated brine. The organic phase was dried over magnesium sulfate, filtered and concentrated under reduced pressure. Purification by crystallization from dichloromethane yielded 1.1 g of the intermediate.

1. stirringthe mixture was stirred at 0° C. for 1 h and at ambient temperature for 0.5 h
2. additionwas added dropwise at −78° C
3. temperatureto warm to room temperature
4. extractionThe mixture was extracted three times with ethyl acetate
5. washthe collected extracts were washed with saturated brine
6. dry with materialThe organic phase was dried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customPurification
10. customby crystallization from dichloromethane

ORD record

ord-f9ec109cf7314885b419abb648abdc3f

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07902379B2