2-Bromoanisole → 3-Hydroxy-3-(2-methoxyphenyl)-5-trifluoromethoxy-1,3-dihydro-2H-indol-2-one

HRID 1593396

Reaction equation

HRID 1593396 reaction equation
[Mg:1].[Br:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[O:9][CH3:10].[F:11][C:12]([F:26])([F:25])[O:13][C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[NH:19][C:18](=[O:23])[C:17]2=[O:24].[NH4+].[Cl-]>CCOCC.C1COCC1>[CH3:12][O:13][C:14]1[CH:15]=[CH:16][CH:20]=[CH:21][C:22]=1[Mg:1][Br:2].[OH:24][C:17]1([C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[O:9][CH3:10])[C:16]2[C:20](=[CH:21][CH:22]=[C:14]([O:13][C:12]([F:11])([F:25])[F:26])[CH:15]=2)[NH:19][C:18]1=[O:23]

Participants

8

Reactant 4

HCID 113582-BromoanisoleHCID 25517Ammonium ChlorideHCID 27327525-(trifluoromethoxy)-2,3-dihydro-1H-indole-2,3-dioneHCID 5462224Magnesium

Product 2

HCID 219058993-Hydroxy-3-(2-methoxyphenyl)-5-trifluoromethoxy-1,3-dihydro-2H-indol-2-oneYield 76.3%HCID 178489560HCID 178489560, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent3×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-methoxyphenylmagnesium bromide is prepared from 1.9 g of magnesium in 4 ml of ether and from a solution of 14.54 g of 1-bromo-2-methoxybenzene in 21 ml of ether. This solution is added drop wise, under an argon atmosphere, to a mixture of 5 g of 5-trifluoromethoxy-1H-indole-2,3-dione in 26 ml of THF, cooled beforehand in an ice bath, and then heated at the reflux point of the ether for 1 hour 30 minutes and allowed to cool to RT. The reaction mixture is poured slowly into saturated NH4Cl solution and extracted with EtOAc, the organic phase is washed with 5% K2CO3 solution, with water and with saturated NaCl solution and dried over Na2SO4, and the solvent is evaporated off under vacuum. 2.8 g of the expected product are obtained.

Workup

  1. additionThis solution is added drop wise
  2. temperaturecooled
  3. custombeforehand in an ice bath
  4. extractionextracted with EtOAc
  5. washthe organic phase is washed with 5% K2CO3 solution, with water and with saturated NaCl solution
  6. dry with materialdried over Na2SO4
  7. customthe solvent is evaporated off under vacuum

Sources & evidence

ORD record
ord-3564bb8751494add800b81fcea59bebe
Source dataset
uspto-grants-2007_11
Patent number
US07297692B2

Linked notes

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