Ethyl bromoacetate → Ethyl 2-[2,4-difluoro-3-[[2-fluoro-3-(3-fluorophenyl)-5-methyl-phenyl]methylamino]phenoxy]acetate

HRID 1771620Notes

Reaction equation

HRID 1771620 reaction equation
[F:1][C:2]1[C:7]([NH:8][CH2:9][C:10]2[CH:15]=[C:14]([CH3:16])[CH:13]=[C:12]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=3)[C:11]=2[F:24])=[C:6]([F:25])[CH:5]=[CH:4][C:3]=1[OH:26].C([O-])([O-])=O.[Na+].[Na+].Br[CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36].C([O-])([O-])=O.[Cs+].[Cs+]>CC(=O)CC.O>[F:1][C:2]1[C:7]([NH:8][CH2:9][C:10]2[CH:15]=[C:14]([CH3:16])[CH:13]=[C:12]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=3)[C:11]=2[F:24])=[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

7

Reactant 4

HCID 7748Ethyl bromoacetate2×HCID 10340Sodium CarbonateHCID 10796Cesium carbonateHCID 894437202,4-Difluoro-3-[[2-fluoro-3-(3-fluorophenyl)-5-methyl-phenyl]methylamino]phenol

Product 1

HCID 89443920Ethyl 2-[2,4-difluoro-3-[[2-fluoro-3-(3-fluorophenyl)-5-methyl-phenyl]methylamino]phenoxy]acetateYield 81%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6569Methyl Ethyl KetoneSolvent

Procedure

To a stirred solution of 2,4-difluoro-3-[[2-fluoro-3-(3-fluorophenyl)-5-methyl-phenyl]methylamino]phenol (100 mg, 0.30 mmol, 1.0 eq) and Na2CO3 (58 mg, 0.60 mmol, 2.0 eq) in 2-butanone (10 mL) was added ethyl bromoacetate (75.1 mg, 0.45 mmol, 1.5 eq). The mixture was stirred at room temperature for 3 h. TLC showed the reaction to be incomplete so Cs2CO3 (50 mg, 0.15 mmol, 0.5 eq) was added and the reaction stirred a further 3 h. TLC showed the reaction was still not finished so ethyl bromoacetate (0.2 mL) was added and the reaction stirred for a further 1 h. The solution was then poured into water and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried (Na2SO4) and evaporated in vacuo. The residue was purified by chromatography (EtOAc:petroleum ether, 0:1 to 1:10) to give the title compound as a solid (100 mg, 81%).

Workup

  1. customthe reaction
  2. additionwas added
  3. stirringthe reaction stirred a further 3 h
  4. additionwas added
  5. stirringthe reaction stirred for a further 1 h
  6. extractionextracted with EtOAc
  7. washThe combined organic extracts were washed with water and brine
  8. dry with materialdried (Na2SO4)
  9. customevaporated in vacuo
  10. customThe residue was purified by chromatography (EtOAc:petroleum ether, 0:1 to 1:10)

Sources & evidence

ORD record
ord-92cda4d7f9c94f1f928729888be2a353
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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