Water → 5-{[1-(2-Chloro-3-fluoro-4-methoxyphenyl)-3,3,3-trifluoro-2-hydroxy-2-(methoxymethyl)propyl]amino}-7-fluoro-1H-quinolin-2-one

HRID 1945112Notes

Reaction equation

HRID 1945112 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[C:6]([O:9][CH3:10])[CH:5]=[CH:4][C:3]=1[CH:11]([NH:19][C:20]1[CH:29]=[C:28]([F:30])[CH:27]=[C:26]2[C:21]=1[CH:22]=[CH:23][C:24](=[O:31])[NH:25]2)[C:12]1([C:15]([F:18])([F:17])[F:16])[CH2:14][O:13]1.[C:32](=O)([O-])[O-:33].[Cs+].[Cs+].O>CO>[Cl:1][C:2]1[C:7]([F:8])=[C:6]([O:9][CH3:10])[CH:5]=[CH:4][C:3]=1[CH:11]([NH:19][C:20]1[CH:29]=[C:28]([F:30])[CH:27]=[C:26]2[C:21]=1[CH:22]=[CH:23][C:24](=[O:31])[NH:25]2)[C:12]([OH:13])([CH2:14][O:33][CH3:32])[C:15]([F:17])([F:16])[F:18]

Participants

5

Reactant 3

HCID 962WaterHCID 10796Cesium carbonateHCID 462221905-{[(2-chloro-3-fluoro-4-methoxyphenyl)(2-trifluoromethyloxiranyl)methyl]amino}-7-fluoro-1H-quinolin-2-one

Product 1

HCID 426014695-{[1-(2-Chloro-3-fluoro-4-methoxyphenyl)-3,3,3-trifluoro-2-hydroxy-2-(methoxymethyl)propyl]amino}-7-fluoro-1H-quinolin-2-oneYield 42.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

2.14 g (4.64 mmol) 5-{[(2-chloro-3-fluoro-4-methoxyphenyl)(2-trifluoromethyl-oxiranyl)methyl]amino}-7-fluoro-1H-quinolin-2-on obtained in example 3 are stirred with 2.57 g (7.9 mmol) Caesium carbonate in 37 ml methanol. After 3 days water is added and the aqueous phase is extracted with ethyl acetate. The combined organic phases are washed with brine and dried over sodium sulphate. After removal of the solvent flash chromatography on silica gel (methanol in dichloromethan 0 to 5%) yields 0.98 g of the title compound.

Workup

  1. extractionthe aqueous phase is extracted with ethyl acetate
  2. washThe combined organic phases are washed with brine
  3. dry with materialdried over sodium sulphate
  4. customAfter removal of the solvent flash chromatography on silica gel (methanol in dichloromethan 0 to 5%)

Sources & evidence

ORD record
ord-48699ed4c2a1416b8e43f33fc744fa79
Source dataset
uspto-grants-2013_03
Patent number
US08394958B2

Reaction notes

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