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

HRID 1771608Notes

Reaction equation

HRID 1771608 reaction equation
[F:1][C:2]1[C:7]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=3)[CH:11]=2)=[C:6]([F:23])[CH:5]=[CH:4][C:3]=1[OH:24].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34]>CC(C)=O>[F:1][C:2]1[C:7]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=3)[CH:11]=2)=[C:6]([F:23])[CH:5]=[CH:4][C:3]=1[O:24][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34]

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 10796Cesium carbonateHCID 894442752,4-Difluoro-3-[[3-(3-fluorophenyl)phenyl]methylamino]phenol

Product 1

HCID 89444317Ethyl 2-[2,4-difluoro-3-[[3-(3-fluorophenyl) phenyl]methylamino]phenoxy]acetateYield 86%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a stirred solution of 2,4-difluoro-3-[[3-(3-fluorophenyl)phenyl]methylamino]phenol (250 mg, 0.76 mmol, 1.0 eq) in acetone (3 mL) was added Cs2CO3 (297 mg, 0.912 mmol, 1.2 eq). The resulting mixture was stirred for 40 min at room temperature then ethyl bromoacetate (139.4 mg, 0.84 mmol, 1.1 eq) was added. The resulting mixture was stirred overnight then partitioned against 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 column chromatography (petroleum ether:EtOAc 1:0 to 20:1) to give the title compound as an oil (270 mg, 86%).

Workup

  1. stirringThe resulting mixture was stirred overnight
  2. customthen partitioned against water
  3. extractionextracted with EtOAc
  4. washThe combined organic extracts were washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. customevaporated in vacuo
  7. customThe residue was purified by column chromatography (petroleum ether:EtOAc 1:0 to 20:1)

Sources & evidence

ORD record
ord-f5026a771f6c4386937b1928f9d7e716
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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