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

HRID 1771767Notes

Reaction equation

HRID 1771767 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([CH3:9])[C:3]=1[NH:10][CH2:11][C:12]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[C:14]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=2)[CH:13]=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:34][C:35]([O:37][CH:38]([CH3:40])[CH3:39])=[O:36].O>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:34][C:35]([O:37][CH:38]([CH3:40])[CH3:39])=[O:36])=[C:4]([CH3:9])[C:3]=1[NH:10][CH2:11][C:12]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[C:14]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=2)[CH:13]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 121593Isopropyl bromoacetateHCID 894440274-Fluoro-3-[[3-(3-fluorophenyl)-5-methoxy-phenyl]methylamino]-2-methyl-phenol

Product 1

HCID 89443840Isopropyl 2-[4-fluoro-3-[[3-(3-fluorophenyl)-5-methoxy-phenyl]methylamino]-2-methyl-phenoxy]acetateYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-fluoro-3-[[3-(3-fluorophenyl)-5-methoxy-phenyl]methylamino]-2-methyl-phenol (390 mg, 1.1 mmol, 1.0 eq) in DMF (6 mL) was added Cs2CO3 (538 mg, 1.65 mmol, 1.5 eq). The reaction was stirred 30 min, then isopropyl 2-bromoacetate (239 mg, 1.32 mmol, 1.2 eq) was added at room temperature. The reaction mixture was stirred at room temperature for a further 1 h, then water was added and the aqueous layer was extracted with EtOAc. The organic extract was washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The crude product was purified by column chromatography (petroleum ether:EtOAc, 1:0, 100:1, to 20:1) to give the title compound as a colorless oil (400 mg, 80%).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for a further 1 h
  2. extractionthe aqueous layer was extracted 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 product was purified by column chromatography (petroleum ether:EtOAc, 1:0, 100:1, to 20:1)

Sources & evidence

ORD record
ord-f446f393ea0b4824a2f739fcd54f7eb1
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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