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

Temperature

-78 °C

A 1.7 M solution of tert-butyllithium in pentane (57.8 mL) was added to THF (200 ml) at −78° C. 2-Bromomesitylene (3.6 mL) was added dropwise, keeping the temperature below −60° C., and the mixture stirred at −78° C. for 1 h. 3-Methoxypyridine (3.6 mL) was added dropwise at −78° C. and then the mixture was allowed to warm to −5° C. over 2 h. The reaction mixture was re-cooled to −78° C. and a slurry of 5-chloroisatin (3.26 g) in THF (100 mL) was added portionwise keeping the temperature below −60° C. The reaction mixture was stirred at −78° C. for 1 h. The cooling bath was removed and the reaction mixture was stirred for 30 min. The reaction mixture was quenched with 10% aqueous ammonium chloride solution and extracted several times with ethyl acetate. The combined organic layers were washed with water, dried over magnesium sulfate and evaporated to low volume. Upon standing, 0.73 g of a pale yellow solid separated which was filtered off, washed with ethyl acetate and dried in vacuo.

1. customthe temperature below −60° C.
2. temperatureto warm to −5° C. over 2 h
3. temperatureThe reaction mixture was re-cooled to −78° C.
4. customthe temperature below −60° C
5. stirringThe reaction mixture was stirred at −78° C. for 1 h
6. customThe cooling bath was removed
7. stirringthe reaction mixture was stirred for 30 min
8. customThe reaction mixture was quenched with 10% aqueous ammonium chloride solution
9. extractionextracted several times with ethyl acetate
10. washThe combined organic layers were washed with water
11. dry with materialdried over magnesium sulfate
12. customevaporated to low volume
13. custom0.73 g of a pale yellow solid separated which
14. filtrationwas filtered off
15. washwashed with ethyl acetate
16. customdried in vacuo

ORD record

ord-7358de44a10043df925ab82ea77fdd1a

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07902379B2