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

HRID 1771648Notes

Reaction equation

HRID 1771648 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[CH:9]=2)=[CH:4][C:3]=1[CH2:15][NH:16][C:17]1[C:18]([F:25])=[C:19]([OH:24])[CH:20]=[CH:21][C:22]=1[F:23].C([O-])([O-])=O.[Cs+].[Cs+].[CH2:32]([O:34][C:35](=[O:38])[CH2:36]Br)[CH3:33].O>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[CH:9]=2)=[CH:4][C:3]=1[CH2:15][NH:16][C:17]1[C:18]([F:25])=[C:19]([CH:20]=[CH:21][C:22]=1[F:23])[O:24][CH2:36][C:35]([O:34][CH2:32][CH3:33])=[O:38]

Participants

6

Reactant 4

HCID 962WaterHCID 7748Ethyl bromoacetateHCID 10796Cesium carbonateHCID 894452343-[[2-Chloro-5-(3-fluorophenyl)phenyl]methylamino]-2,4-di fluoro-phenol

Product 1

HCID 89443391Ethyl 2-[3-[[2-chloro-5-(3-fluorophenyl)phenyl]methylamino]-2,4-difluoro-phenoxy]acetateYield 76.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-[[2-chloro-5-(3-fluorophenyl)phenyl]methylamino]-2,4-difluoro-phenol (128 mg, 0.35 mmol, 1.0 eq) in DMF (10 mL) was added Cs2CO3 (172 mg, 0.53 mmol, 1.5 eq). The reaction was stirred at room temperature for 30 min then ethylbromoacetate (70.5 mg, 0.42 mmol, 1.2 eq) was added dropwise. The reaction was stirred at room temperature for further 3 h then water was added and the aqueous layer extracted with EtOAc. The organic extract was washed with water and brine, dried (Na2SO4), filtered, evaporated in vacuo and the residue obtained purified by chromatography (petroleum ether:EtOAc, 100:1 to 20:1) to give the title compound as a colourless oil (120 mg, 76%).

Workup

  1. stirringThe reaction was stirred at room temperature for further 3 h
  2. extractionthe aqueous layer extracted with EtOAc
  3. extractionThe organic extract
  4. washwas washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customthe residue obtained
  9. custompurified by chromatography (petroleum ether:EtOAc, 100:1 to 20:1)

Sources & evidence

ORD record
ord-c0e95bb7a5194c7baa3ec8e2feeb8478
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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