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

HRID 1771759Notes

Reaction equation

HRID 1771759 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]=[C:14]([CH3:25])[C:13]=1[O:26][CH3:27].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:35][C:36]([O:38][CH:39]([CH3:41])[CH3:40])=[O:37].O>CC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:35][C:36]([O:38][CH:39]([CH3:41])[CH3:40])=[O:37])=[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]=[C:14]([CH3:25])[C:13]=1[O:26][CH3:27]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 121593Isopropyl bromoacetateHCID 894436934-Fluoro-3-[[5-(3-fluorophenyl)-2-methoxy-3-methyl-phenyl]methylamino]-2-methyl-phenol

Product 1

HCID 89445418Isopropyl 2-[4-fluoro-3-[[5-(3-fluorophenyl)-2-methoxy-3-methyl-phenyl]methylamino]-2-methyl-phenoxy]acetateYield 55.4%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a solution of 4-fluoro-3-[[5-(3-fluorophenyl)-2-methoxy-3-methyl-phenyl]methylamino]-2-methyl-phenol (94 mg, 0.25 mmol, 1.0 eq) in acetone (4 mL) at room temperature was added Cs2CO3 (124.4 mg, 0.38 mmol, 1.5 eq). The reaction mixture was stirred for 30 min, then isopropyl bromoacetate (55.3 mg, 1.2 mmol, 1.2 eq) was added and stirring continued for a further 2 h. Water was added and the aqueous layer extracted with EtOAc. The organic extract was washed with water and brinc, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by column chromatography (petroleum ether:EtOAc, 20:1) to give the title compound as a colorless oil (65 mg, 54%).

Workup

  1. stirringstirring
  2. waitcontinued for a further 2 h
  3. extractionthe aqueous layer extracted with EtOAc
  4. extractionThe organic extract
  5. washwas washed with water and brinc
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe residue was purified by column chromatography (petroleum ether:EtOAc, 20:1)

Sources & evidence

ORD record
ord-1e39ad4f4dce46428f0a0995361988c4
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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