Water → Ethyl 2-[2,4-difluoro-3-[[6-fluoro-3-(3-fluorophenyl)-2-methyl-phenyl]methylamino]phenoxy]acetate

HRID 1771723Notes

Reaction equation

HRID 1771723 reaction equation
[F:1][C:2]1[C:7]([NH:8][CH2:9][C:10]2[C:15]([F:16])=[CH:14][CH:13]=[C:12]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=3)[C:11]=2[CH3:24])=[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[C:15]([F:16])=[CH:14][CH:13]=[C:12]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=3)[C:11]=2[CH3:24])=[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

6

Reactant 4

HCID 962WaterHCID 7748Ethyl bromoacetateHCID 10796Cesium carbonateHCID 894438562,4-Difluoro-3-[[6-fluoro-3-(3-fluorophenyl)-2-methyl-phenyl]methylamino]phenol

Product 1

HCID 89444025Ethyl 2-[2,4-difluoro-3-[[6-fluoro-3-(3-fluorophenyl)-2-methyl-phenyl]methylamino]phenoxy]acetateYield 85.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2,4-difluoro-3-[[6-fluoro-3-(3-fluorophenyl)-2-methyl-phenyl]methylamino]phenol (230 mg, 0.63 mmol, 1.0 eq) in DMF (4 mL) was added Cs2CO3 (420 mg, 1.2 mmol, 2 eq). The reaction was stirred for 10 min, then ethyl bromoacetate (130 mg, 0.76 mmol, 1.2 eq) was added. The reaction mixture was stirred for a further 30 min, then water was added and the aqueous layer was extracted with EtOAc. The combined organic extracts were washed with water, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by column chromatography (petroleum ether: EtOAc, 25:1) to give title compound as a colourless oil (240 mg, 85%).

Workup

  1. stirringThe reaction mixture was stirred for a further 30 min
  2. extractionthe aqueous layer was extracted with EtOAc
  3. washThe combined organic extracts were washed with water
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was purified by column chromatography (petroleum ether: EtOAc, 25:1)

Sources & evidence

ORD record
ord-2c0f48d6e82b4a76a369304aea48abcf
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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