Diethyl Ether → 5-Chloro-3-hydroxy-3-(2-methoxyphenyl)indolin-2-one

HRID 983516Notes

Reaction equation

HRID 983516 reaction equation
[Mg:1].[Br:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[O:9][CH3:10].[Cl:11][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[NH:17][C:16](=[O:21])[C:15]2=[O:22].[NH4+].[Cl-].CC[O:27][CH2:28]C>C1COCC1>[CH3:28][O:27][C:12]1[CH:13]=[CH:14][CH:18]=[CH:19][C:20]=1[Mg:1][Br:2].[Cl:11][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[NH:17][C:16](=[O:21])[C:15]2([OH:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[O:9][CH3:10]

Participants

8

Reactant 5

HCID 3283Diethyl Ether2×HCID 113582-BromoanisoleHCID 25517Ammonium ChlorideHCID 872035-chloro-1H-indole-2,3-dioneHCID 5462224Magnesium

Product 2

HCID 219059555-Chloro-3-hydroxy-3-(2-methoxyphenyl)indolin-2-oneHCID 178489560HCID 178489560, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

This compound is prepared according to the procedure disclosed in WO 95/18105. A solution of 2-methoxyphenylmagnesium bromide is prepared from 16 g of magnesium in 35 ml of ether and from a solution of 124 g of 1-bromo-2-methoxybenzene in 175 ml of ether. This solution is added dropwise under an argon atmosphere to a mixture, cooled beforehand in an ice bath, of 30 g of 5-chloro-1H-indole-2,3-dione in 250 ml of THF and then the mixture is left stirring while allowing the temperature to rise to RT. After stirring for 1 hour at RT, the reaction mixture is slowly poured into saturated NH4Cl solution and the THF is evaporated off under vacuum. The precipitate formed is spin-filtered off and is washed with iso ether. 42 g of the expected product are obtained, which product is used without further purification in the following stage.

Workup

  1. customThis compound is prepared
  2. additionThis solution is added dropwise under an argon atmosphere to a mixture
  3. temperaturecooled
  4. waitthe mixture is left
  5. customto rise to RT
  6. stirringAfter stirring for 1 hour at RT
  7. customthe THF is evaporated off under vacuum
  8. customThe precipitate formed
  9. filtrationis spin-filtered off
  10. washis washed with iso ether

Sources & evidence

ORD record
ord-a19840a9385e4f4b94ed0bb3391d99e1
Source dataset
uspto-grants-2005_03
Patent number
US06864277B2

Reaction notes

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