Water → Isopropyl 2-[2,4-difluoro-3-[[3-(3-fluorophenyl)-5-methoxy-phenyl]methylamino]phenoxy]acetate

HRID 1771782Notes

Reaction equation

HRID 1771782 reaction equation
[F:1][C:2]1[C:7]([NH:8][CH2:9][C:10]2[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[C:12]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=3)[CH:11]=2)=[C:6]([F:25])[CH:5]=[CH:4][C:3]=1[OH:26].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:34][C:35]([O:37][CH:38]([CH3:40])[CH3:39])=[O:36].O>CN(C=O)C>[F:1][C:2]1[C:7]([NH:8][CH2:9][C:10]2[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[C:12]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=3)[CH:11]=2)=[C:6]([F:25])[CH:5]=[CH:4][C:3]=1[O:26][CH2:34][C:35]([O:37][CH:38]([CH3:40])[CH3:39])=[O:36]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 121593Isopropyl bromoacetateHCID 894440932,4-Difluoro-3-[[3-(3-fluorophenyl)-5-methoxy-phenyl]methylamino]phenol

Product 1

HCID 89443593Isopropyl 2-[2,4-difluoro-3-[[3-(3-fluorophenyl)-5-methoxy-phenyl]methylamino]phenoxy]acetateYield 62.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2,4-difluoro-3-[[3-(3-fluorophenyl)-5-methoxy-phenyl]methylamino]phenol (see example 16) (1.0 g, 2.78 mmol, 1.0 eq) in DMF (10 mL) was added Cs2CO3 (1.36 g, 3.34 mmol, 1.5 eq) at room temperature. The reaction mixture was stirred for 1 h, then isopropyl 2-bromoacetate (624 mg, 3.34 mmol, 1.2 eq) was added and the reaction mixture was stirred for h. The resulting mixture was poured into water and extracted with EtOAc. The organic extract was washed with water and brine, dried (Na2SO4) and evaporated in vacuo. The residue obtained was purified by column chromatography, (EtOAc:petroleum ether 0:1 to 1:20) to give the title compound as a colourless oil (0.8 g, 62%).

Workup

  1. stirringthe reaction mixture was stirred for h
  2. extractionextracted with EtOAc
  3. extractionThe organic extract
  4. washwas washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. customevaporated in vacuo
  7. customThe residue obtained
  8. customwas purified by column chromatography, (EtOAc:petroleum ether 0:1 to 1:20)

Sources & evidence

ORD record
ord-93b17936c9624e26a0aea035fa2795a9
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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