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

HRID 1771755Notes

Reaction equation

HRID 1771755 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]([CH3:18])[CH:15]=[C:14]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[CH:20]=2)[CH:13]=1.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]([CH3:18])[CH:15]=[C:14]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[CH:20]=2)[CH:13]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 121593Isopropyl bromoacetateHCID 894435214-Fluoro-3-[[3-(3-fluorophenyl)-5-methyl-phenyl]methylamino]-2-methyl-phenol

Product 1

HCID 89443834Isopropyl 2-[4-fluoro-3-[[3-(3-fluorophenyl)-5-methyl-phenyl]methylamino]-2-methyl-phenoxy]acetateYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-fluoro-3-[[3-(3-fluorophenyl)-5-methyl-phenyl]methylamino]-2-methyl-phenol (324 mg, 0.95 mmol, 1.0 eq) in DMF (15 mL) was added Cs2CO3 (467 mg, 1.43 mmol, 1.5 eq). The reaction mixture was stirred at room temperature for 30 min, then isopropyl bromoacetate (207 mg, 1.15 mmol, 1.2 eq) was added and stirring continued for a further 1 h. Water was added and the aqueous layer was extracted with EtOAc. The organic extract was washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue obtained was purified by column chromatography (petroleum ether:EtOAc, 50:1 to 40:1) to give the title compound as a colorless oil (317 mg, 76%).

Workup

  1. stirringstirring
  2. waitcontinued for a further 1 h
  3. extractionthe aqueous layer was extracted with EtOAc
  4. extractionThe organic extract
  5. washwas washed with water and brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe residue obtained
  10. customwas purified by column chromatography (petroleum ether:EtOAc, 50:1 to 40:1)

Sources & evidence

ORD record
ord-0d831e76b35f46fc92be7c615e54f3b1
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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