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

HRID 1771674Notes

Reaction equation

HRID 1771674 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][CH2:38][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][CH2:38][CH3:39])=[O:36]

Participants

6

Reactant 4

HCID 962WaterHCID 7748Ethyl bromoacetateHCID 10796Cesium carbonateHCID 894440932,4-Difluoro-3-[[3-(3-fluorophenyl)-5-methoxy-phenyl]methylamino]phenol

Product 1

HCID 89443604Ethyl 2-[2,4-difluoro-3-[[3-(3-fluorophenyl)-5-methoxy-phenyl]methylamino]phenoxy]acetateYield 80.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2,4-difluoro-3-[[3-(3-fluorophenyl)-5-methoxy-phenyl]methylamino]phenol (500 mg, 1.4 mmol, 1.0 eq) in DMF (10 mL) was added Cs2CO3 (634 mg, 1.9 mmol, 1.4 eq). The reaction mixture was stirred for 1 h, then ethyl 2-bromoacetate (279 mg, 1.7 mmol, 1.2 eq) was added. The reaction mixture was stirred for a further 1 h, then poured into water and extracted with EtOAc. The organic extract was washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The crude residue obtained was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:10) to give the title compound as an oil (500 mg, 80%).

Workup

  1. stirringThe reaction mixture 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 crude residue obtained
  9. customwas purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:10)

Sources & evidence

ORD record
ord-4474b31c0c7d44d0834444d47d65a9f3
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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