Lithium hydroxide, monohydrate → 3-{[2-Fluoro-1-(fluoromethyl)ethyl]oxy}-5-[(phenylmethyl)oxy]benzoic acid

HRID 1011706Notes

Reaction equation

HRID 1011706 reaction equation
O.[OH-].[Li+].[F:4][CH2:5][CH:6]([O:9][C:10]1[CH:11]=[C:12]([CH:17]=[C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:19]=1)[C:13]([O:15]C)=[O:14])[CH2:7][F:8]>O.C1COCC1>[F:4][CH2:5][CH:6]([O:9][C:10]1[CH:11]=[C:12]([CH:17]=[C:18]([O:20][CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:19]=1)[C:13]([OH:15])=[O:14])[CH2:7][F:8]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 59127098Methyl 3-(benzyloxy)-5-(1,3-difluoropropan-2-yloxy)benzoate

Product 1

HCID 591271423-{[2-Fluoro-1-(fluoromethyl)ethyl]oxy}-5-[(phenylmethyl)oxy]benzoic acidYield 90.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of lithium hydroxide monohydrate (2.32 g, 55.1 mmol) in water (100 mL) was added to a solution of methyl 3-{[2-fluoro-1-(fluoromethyl)ethyl]oxy}-5-[(phenylmethyl)oxy]benzoate (7.41 g, 22.0 mmol) in THF (200 mL) and the mixture allowed to stir at RT overnight. The THF was removed in vacuo and the resulting solution partitioned between water (100 mL) and ethyl acetate (250 mL). The ethyl acetate layer was separated, washed with brine and dried (MgSO4). The aqueous layer was then adjusted to pH 7 by addition of 1M hydrochloric acid and extracted with ethyl acetate (75 mL). The ethyl acetate layer was separated, washed with brine and dried (MgSO4). The ethyl acetate layers were combined and evaporated to give the required product (6.404 g).

Workup

  1. customThe THF was removed in vacuo
  2. customthe resulting solution partitioned between water (100 mL) and ethyl acetate (250 mL)
  3. customThe ethyl acetate layer was separated
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. additionThe aqueous layer was then adjusted to pH 7 by addition of 1M hydrochloric acid
  7. extractionextracted with ethyl acetate (75 mL)
  8. customThe ethyl acetate layer was separated
  9. washwashed with brine
  10. dry with materialdried (MgSO4)
  11. customevaporated

Sources & evidence

ORD record
ord-8d4a4b71d27848429fa091037c0c11dd
Source dataset
uspto-grants-2011_07
Patent number
US07977328B2

Reaction notes

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