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

HRID 1771772Notes

Reaction equation

HRID 1771772 reaction equation
[F:1][C:2]1[C:12]([NH:13][CH2:14][C:15]2[CH:20]=[C:19]([CH3:21])[CH:18]=[C:17]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[CH:23]=3)[C:16]=2[F:29])=[C:11]([F:30])[CH:10]=[CH:9][C:3]=1[O:4][CH2:5][C:6]([OH:8])=[O:7].C([O-])([O-])=O.[Cs+].[Cs+].BrCC(O[CH:42]([CH3:44])[CH3:43])=O.O>CN(C=O)C>[F:1][C:2]1[C:12]([NH:13][CH2:14][C:15]2[CH:20]=[C:19]([CH3:21])[CH:18]=[C:17]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[CH:23]=3)[C:16]=2[F:29])=[C:11]([F:30])[CH:10]=[CH:9][C:3]=1[O:4][CH2:5][C:6]([O:8][CH:42]([CH3:44])[CH3:43])=[O:7]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 121593Isopropyl bromoacetateHCID 715155172-[2,4-Difluoro-3-[[2-fluoro-3-(3-fluorophenyl)-5-methyl-phenyl]methylamino]phenoxy]acetic acid

Product 1

HCID 89467101Isopropyl 2-[2,4-difluoro-3-[[2-fluoro-3-(3-fluorophenyl)-5-methyl-phenyl]methylamino]phenoxy]acetateYield 81%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-[2,4-difluoro-3-[[2-fluoro-3-(3-fluorophenyl)-5-methyl-phenyl]methylamino]phenoxy]acetic acid (I(g)) (300 mg, 0.83 mmol, 1.0 eq) and Cs2CO3 (407 mg, 1.25 mmol, 1.5 eq) in DMF (5 mL) was stirred at room temperature for 1 h, then isopropyl bromoacetate (171 mg, 0.91 mmol, 1.1 eq) was added. The mixture was stirred at room temperature for 1 h. The resulting mixture was poured into water and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:10) to give the title compound as an oil (310 mg, 81%).

Workup

  1. stirringThe mixture was stirred at room temperature for 1 h
  2. extractionextracted with EtOAc
  3. washThe combined organic extracts were washed with water and brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:10)

Sources & evidence

ORD record
ord-5b8b09ebe34640a7bab0e948a14bed32
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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