Benzothiazole → 3-Benzothiazol-2-yl-5-chloro-3-hydroxy-1,3-dihydroindol-2-one

Temperature

-78 °C

A 1.6 M solution of n-butyllithium in hexane (35 ml, 56 mmol) was added dropwise to a solution of benzothiazole (6.2 ml, 56 mmol) in THF (100 ml) at −78° C. After stirring at −78° C. for 1.5 h, the solution of the lithiated benzothiazole was transferred via a needle into an ice-cold suspension of 5-chloroisatin (3.63 g, 20 mmol) in THF (70 ml). The reaction mixture was stirred at 0° C. for 1 h and then saturated ammonium chloride solution was added. The mixture was extracted three times with ethyl acetate and the combined organic layers were washed with saturated brine. The organic phase was dried over magnesium sulfate, filtered and concentrated under reduced pressure, during which the intermediate starts to crystallize. Filtration and drying yielded 4.47 g of the intermediate as yellow crystalline solid.

1. stirringThe reaction mixture was stirred at 0° C. for 1 h
2. extractionThe mixture was extracted three times with ethyl acetate
3. washthe combined organic layers were washed with saturated brine
4. dry with materialThe organic phase was dried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure, during which the intermediate starts
7. customto crystallize
8. filtrationFiltration
9. customdrying

ORD record

ord-e5eae028b60e4c4ea8c9ba5242290edb

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08580842B2