Lithium hydroxide, monohydrate → 2-[2,4-Difluoro-3-[[2-fluoro-3-(3-fluorophenyl)-5-methyl-phenyl]methylamino]phenoxy]acetic acid

HRID 1771621Notes

Reaction equation

HRID 1771621 reaction equation
[F:1][C:2]1[C:14]([NH:15][CH2:16][C:17]2[CH:22]=[C:21]([CH3:23])[CH:20]=[C:19]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=3)[C:18]=2[F:31])=[C:13]([F:32])[CH:12]=[CH:11][C:3]=1[O:4][CH2:5][C:6]([O:8]CC)=[O:7].O[Li].O>C1COCC1.O>[F:1][C:2]1[C:14]([NH:15][CH2:16][C:17]2[CH:22]=[C:21]([CH3:23])[CH:20]=[C:19]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=3)[C:18]=2[F:31])=[C:13]([F:32])[CH:12]=[CH:11][C:3]=1[O:4][CH2:5][C:6]([OH:8])=[O:7]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 89443920Ethyl 2-[2,4-difluoro-3-[[2-fluoro-3-(3-fluorophenyl)-5-methyl-phenyl]methylamino]phenoxy]acetate

Product 1

HCID 715155172-[2,4-Difluoro-3-[[2-fluoro-3-(3-fluorophenyl)-5-methyl-phenyl]methylamino]phenoxy]acetic acidYield 35.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of ethyl 2-[2,4-difluoro-3-[[2-fluoro-3-(3-fluorophenyl)-5-methyl-phenyl]methylamino]phenoxy]acetate (100 mg, 0.2 mmol, 1.0 eq) in a mixture of THF (20 mL) and water (20 mL) was added LiOH.H2O (38 mg, 0.9 mmol, 4.0 eq). The reaction was stirred at room temperature for 2 h. The THF was then removed in vacuo and the aqueous residue acidified by addition of 1M HCl and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue obtained was washed with a mixture of petroleum ether: EtOAc, 10:1 to give the title compound (I(g)) as white solid (30 mg, 32%).

Workup

  1. customThe THF was then removed in vacuo
  2. additionthe aqueous residue acidified by addition of 1M HCl
  3. extractionextracted with EtOAc
  4. washThe combined organic extracts were washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe residue obtained
  9. washwas washed with a mixture of petroleum ether

Sources & evidence

ORD record
ord-abfae573afed4a64ae5dd8f997ff239e
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

Loading…