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

HRID 601765

Reaction equation

HRID 601765 reaction equation
C([Li])(C)(C)C.BrC1C(C)=CC(C)=CC=1C.[CH3:16][O:17][C:18]1[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=1.[Cl:24][C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[NH:30][C:29](=[O:34])[C:28]2=[O:35]>CCCCC.C1COCC1>[Cl:24][C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[NH:30][C:29](=[O:34])[C:28]2([OH:35])[C:19]1[C:18]([O:17][CH3:16])=[CH:23][CH:22]=[CH:21][N:20]=1

Participants

7

Reactant 4

HCID 237193-MethoxypyridineHCID 684732-BromomesityleneHCID 872035-chloro-1H-indole-2,3-dioneHCID 178418306HCID 178418306, compound

Product 1

HCID 575177605-Chloro-3-hydroxy-3-(3-methoxy-pyridin-2-yl)-1,3-dihydro-indol-2-one

Reagents, catalysts & solvents 2

HCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

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 stirred between −30° C. and −20° C. 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, 1.05 g of a cream-colored solid separated which was filtered off, washed with ethyl acetate and dried in vacuo.

Workup

  1. customthe temperature below −60° C.
  2. stirringthe mixture was stirred between −30° C. and −20° C
  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. custom1.05 g of a cream-colored solid separated which
  14. filtrationwas filtered off
  15. washwashed with ethyl acetate
  16. customdried in vacuo

Sources & evidence

ORD record
ord-147a4bc83edf47938af5cb28e064f44c
Source dataset
uspto-grants-2011_03
Patent number
US07902379B2

Linked notes

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