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

HRID 1593394Notes

Reaction equation

HRID 1593394 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 drop wise, under an argon atmosphere, to a mixture of 30 g of 5-chloro-1H-indole-2,3-dione in 250 ml of THF, cooled beforehand in a bath of ice, and the mixture is then left stirring while allowing the temperature to return to RT. After stirring for one hour at RT, the reaction mixture is poured slowly into saturated NH4Cl solution and the THF is evaporated off under vacuum. The precipitate formed is spin-filtered off and washed with iso-ether. 42 g of the expected product are obtained and are used in the next step without further purification.

Workup

  1. customThis compound is prepared
  2. additionThis solution is added drop wise
  3. temperaturecooled
  4. custombeforehand in a bath of ice
  5. waitthe mixture is then left
  6. customto return to RT
  7. stirringAfter stirring for one hour at RT
  8. customthe THF is evaporated off under vacuum
  9. customThe precipitate formed
  10. filtrationis spin-filtered off
  11. washwashed with iso-ether

Sources & evidence

ORD record
ord-0e2396e4752743d38c3bec9073c774f3
Source dataset
uspto-grants-2007_11
Patent number
US07297692B2

Reaction notes

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