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

HRID 1771775Notes

Reaction equation

HRID 1771775 reaction equation
[F:1][C:2]1[C:15]([NH:16][CH2:17][C:18]2[CH:23]=[C:22]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=3)[CH:21]=[CH:20][C:19]=2[F:31])=[C:14]([F:32])[CH:13]=[CH:12][C:3]=1[O:4][CH2:5][C:6]([O:8][CH:9](C)[CH3:10])=[O:7].[OH:33]S(O)(=O)=O.O>C(O)CO>[F:1][C:2]1[C:15]([NH:16][CH2:17][C:18]2[CH:23]=[C:22]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=3)[CH:21]=[CH:20][C:19]=2[F:31])=[C:14]([F:32])[CH:13]=[CH:12][C:3]=1[O:4][CH2:5][C:6]([O:8][CH2:9][CH2:10][OH:33])=[O:7]

Participants

5

Reactant 3

HCID 962WaterHCID 1118Sulfuric AcidHCID 71503443US9249085, II(d)

Product 1

HCID 894454422-Hydroxyethyl 2-[2,4-difluoro-3-[[2-fluoro-5-(3-fluorophenyl)phenyl]methylamino]phenoxy]acetate

Reagents, catalysts & solvents 1

HCID 174Ethylene GlycolSolvent

Conditions

Temperature
10 °C

Procedure

To a solution of isopropyl 2-[2,4-difluoro-3-[[2-fluoro-5-(3-fluorophenyl)phenyl]methylamino]phenoxy]acetate (II(d)) (0.63 g, 1.41 mmol, 1.0 eq) in ethylene glycol (30 mL) at room temperature was added H2SO4 (0.4 mL, 7.5 mmol, 5.3 eq) dropwise. The reaction mixture was stirred overnight at 10° C. then heated at 40° C. for 3 h. The reaction was then cooled to room temperature and poured into water. The aqueous layer was extracted with EtOAc and the combined organic extracts were washed with 5% Na2CO3, water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by column chromatography (EtOAc:petroleum ether, 1:5 to 1:1) to give the title compound as an oil, which crystallised on standing to give a white solid (0.54 g, 85%).

Workup

  1. temperaturethen heated at 40° C. for 3 h
  2. temperatureThe reaction was then cooled to room temperature
  3. extractionThe aqueous layer was extracted with EtOAc
  4. washthe combined organic extracts were washed with 5% Na2CO3, water and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe residue was purified by column chromatography (EtOAc:petroleum ether, 1:5 to 1:1)

Sources & evidence

ORD record
ord-76f2f84a501f4b33b3eaf3b350fc38fe
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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