Potassium Carbonate → 1-Acetoxyethyl 2-[2,4-difluoro-3-[[2-fluoro-5-(3-fluorophenyl)phenyl]methylamino]phenoxy]acetate

HRID 1771781Notes

Reaction equation

HRID 1771781 reaction equation
[C:1]([O:4][CH:5](Br)[CH3:6])(=[O:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].[F:14][C:15]1[C:25]([NH:26][CH2:27][C:28]2[CH:33]=[C:32]([C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[CH:35]=3)[CH:31]=[CH:30][C:29]=2[F:41])=[C:24]([F:42])[CH:23]=[CH:22][C:16]=1[O:17][CH2:18][C:19]([OH:21])=[O:20]>CC(N(C)C)=O>[F:14][C:15]1[C:25]([NH:26][CH2:27][C:28]2[CH:33]=[C:32]([C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[CH:35]=3)[CH:31]=[CH:30][C:29]=2[F:41])=[C:24]([F:42])[CH:23]=[CH:22][C:16]=1[O:17][CH2:18][C:19]([O:21][CH:5]([O:4][C:1](=[O:3])[CH3:2])[CH3:6])=[O:20]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 111375051-Bromoethyl acetateHCID 715155142-[2,4-Difluoro-3-[[2-fluoro-5-(3-fluorophenyl)phenyl]methylamino]phenoxy]acetic acid

Product 1

HCID 894440031-Acetoxyethyl 2-[2,4-difluoro-3-[[2-fluoro-5-(3-fluorophenyl)phenyl]methylamino]phenoxy]acetateYield 23.9%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
30 °C

Procedure

1-bromoethyl acetate (700 mg, 1.7 mmol, 1.0 eq) was dissolved in DMA (10 mL) at room temperature. K2CO3 (120 mg, 0.9 mmol, 0.5 mmol) was added and the mixture stirred for 90 min at 30° C. under a nitrogen atmosphere. The reaction was cooled to −5° C. and 2-[2,4-difluoro-3-[[2-fluoro-5-(3-fluorophenyl)phenyl]methylamino]phenoxy]acetic acid (I(b)) (350 mg, 2.1 mmol, 1.2 eq) was added. The reaction was warmed to 30° C. over 30 min and stirred for a further 30 min. The reaction was quenched by addition of water and extracted with ethyl acetate. The organic extract was dried (Na2SO4), filtered and evaporated in vacuo and the residue obtained purified by column chromatography (petroleum ether: EtOAc, 10:1) to give the title compound as a colourless oil (200 mg, 23%).

Workup

  1. temperatureThe reaction was cooled to −5° C.
  2. temperatureThe reaction was warmed to 30° C. over 30 min
  3. stirringstirred for a further 30 min
  4. customThe reaction was quenched by addition of water
  5. extractionextracted with ethyl acetate
  6. extractionThe organic extract
  7. dry with materialwas dried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated in vacuo
  10. customthe residue obtained
  11. custompurified by column chromatography (petroleum ether: EtOAc, 10:1)

Sources & evidence

ORD record
ord-e171874f0236421ab42b3bf15eef6b51
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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