Water → Isopropyl 2-[4-fluoro-3-[[2-fluoro-5-(3-fluorophenyl)phenyl]methylamino]-2-methyl-phenoxy]acetate

HRID 1771774Notes

Reaction equation

HRID 1771774 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([CH3:9])[C:3]=1[NH:10][CH2:11][C:12]1[CH:17]=[C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=2)[CH:15]=[CH:14][C:13]=1[F:25].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:33][C:34]([O:36][CH:37]([CH3:39])[CH3:38])=[O:35].O>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:33][C:34]([O:36][CH:37]([CH3:39])[CH3:38])=[O:35])=[C:4]([CH3:9])[C:3]=1[NH:10][CH2:11][C:12]1[CH:17]=[C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=2)[CH:15]=[CH:14][C:13]=1[F:25]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 121593Isopropyl bromoacetateHCID 894453134-Fluoro-3-[[2-fluoro-5-(3-fluorophenyl)phenyl]methylamino]-2-methyl-phenol

Product 1

HCID 89443660Isopropyl 2-[4-fluoro-3-[[2-fluoro-5-(3-fluorophenyl)phenyl]methylamino]-2-methyl-phenoxy]acetateYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-fluoro-3-[[2-fluoro-5-(3-fluorophenyl)phenyl]methylamino]-2-methyl-phenol (see example 13) (150 mg, 0.44 mmol, 1.0 eq) in DMF (2 mL) was added Cs2CO3 (214 mg, 0.66 mmol, 1.5 eq) and the reaction mixture was stirred for 1 h. Isopropyl 2-bromoacetate (80 mg, 0.44 mmol, 1.0 eq) was then added and the reaction was stirred for a further 1 h. The resulting mixture was poured into water and extracted with EtOAc. The organic extract was washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:20) to give the title compound as a colourless oil (130 mg, 80%).

Workup

  1. stirringthe reaction was stirred for a further 1 h
  2. extractionextracted 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 was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:20)

Sources & evidence

ORD record
ord-bf6d97183bb644929acce369b744298a
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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