Lithium Hydroxide → 2-[2-Chloro-4-fluoro-3-[[2-fluoro-5-(3-fluorophenyl)phenyl]methylamino]phenoxy]acetic acid

HRID 1771668Notes

Reaction equation

HRID 1771668 reaction equation
[Cl:1][C:2]1[C:14]([NH:15][CH2:16][C:17]2[CH:22]=[C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=3)[CH:20]=[CH:19][C:18]=2[F:30])=[C:13]([F:31])[CH:12]=[CH:11][C:3]=1[O:4][CH2:5][C:6]([O:8]CC)=[O:7].[Li+].[OH-]>C1COCC1>[Cl:1][C:2]1[C:14]([NH:15][CH2:16][C:17]2[CH:22]=[C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=3)[CH:20]=[CH:19][C:18]=2[F:30])=[C:13]([F:31])[CH:12]=[CH:11][C:3]=1[O:4][CH2:5][C:6]([OH:8])=[O:7]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 89444345Ethyl 2-[2-chloro-4-fluoro-3-[[2-fluoro-5-(3-fluorophenyl)phenyl]methylamino]phenoxy]acetate

Product 1

HCID 894441212-[2-Chloro-4-fluoro-3-[[2-fluoro-5-(3-fluorophenyl)phenyl]methylamino]phenoxy]acetic acidYield 69.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 2-[2-chloro-4-fluoro-3-[[2-fluoro-5-(3-fluorophenyl)phenyl]methylamino]phenoxy]acetate (155 mg, 0.34 mmol) in THF (2 mL) was added LiOH (2M aqueous solution, 2.5 mL, 2.5 mmol, 7.4 eq). The reaction mixture was stirred at room temperature for 2 h, then the organic solvent was removed in vacuo. The residue that remained was diluted with water and adjusted to pH 4-6 by addition of diluted HCl. The solid precipitate that formed was collected by filtration, washed with water and dried in vacuo to afford a crude product which was crystallized from DCM (1 mL) and hexane (20 mL) to give the title compound (I(o)) as a white solid (100 mg, 69%).

Workup

  1. customthe organic solvent was removed in vacuo
  2. additionThe residue that remained was diluted with water
  3. additionadjusted to pH 4-6 by addition of diluted HCl
  4. customThe solid precipitate that formed
  5. filtrationwas collected by filtration
  6. washwashed with water
  7. customdried in vacuo
  8. customto afford a crude product which
  9. customwas crystallized from DCM (1 mL) and hexane (20 mL)

Sources & evidence

ORD record
ord-97311fa88b0b40979c13d95012d42ee6
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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