Hydrochloric Acid → 2-{3-Chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-5-yl)-propyl]-phenoxy}-2-methyl-propionic acid

HRID 2096903Notes

Reaction equation

HRID 2096903 reaction equation
C([O:3][C:4](=[O:35])[C:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([CH3:33])[C:16]([OH:32])([C:21]2[CH:22]=[CH:23][C:24]3[O:28][C:27](=[O:29])[N:26]([CH3:30])[C:25]=3[CH:31]=2)[C:17]([F:20])([F:19])[F:18])=[C:11]([Cl:34])[CH:10]=1)([CH3:7])[CH3:6])C.[Li+].[OH-].O.Cl>C1COCC1>[Cl:34][C:11]1[CH:10]=[C:9]([CH:14]=[CH:13][C:12]=1[CH:15]([CH3:33])[C:16]([OH:32])([C:21]1[CH:22]=[CH:23][C:24]2[O:28][C:27](=[O:29])[N:26]([CH3:30])[C:25]=2[CH:31]=1)[C:17]([F:19])([F:18])[F:20])[O:8][C:5]([CH3:6])([CH3:7])[C:4]([OH:35])=[O:3]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 3939Lithium Hydroxide2×HCID 666970582-{3-Chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-5-yl)-propyl]-phenoxy}-2-methyl-propionic acid ethyl ester

Product 1

HCID 666970612-{3-Chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-5-yl)-propyl]-phenoxy}-2-methyl-propionic acidYield 16%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-{3-Chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-5-yl)-propyl]-phenoxy}-2-methyl-propionic acid ethyl ester (99 mg, obtained in Example 229) was dissolved in THF (2.3 mL) under argon. LiOH solution (1M, 0.31 mL) was added and the mixture was stirred for 3 hours. Another 0.19 mL of the LiOH solution was added and stirring was continued at r.t. for 48 hours. The reaction mixture was poured into water containing ice and the aqueous solution was acidified with 1M HCl to pH 1. The aqueous mixture was extracted with ethyl acetate and the organic extracts were washed with brine, dried over Na2SO4 and evaporated. The residue was purified by flash chromatography (silica gel, ethyl acetate, then ethyl acetate containing 0.25% acetic acid) to provide the title compound 2-{3-chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-5-yl)-propyl]-phenoxy}-2-methyl-propionic acid as a light brown foam (15 mg). MS (m/e, ISP neg. ion)=486.5 [M−H+].

Workup

  1. stirringstirring
  2. waitwas continued at r.t. for 48 hours
  3. additioncontaining ice
  4. extractionThe aqueous mixture was extracted with ethyl acetate
  5. washthe organic extracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. customThe residue was purified by flash chromatography (silica gel, ethyl acetate

Sources & evidence

ORD record
ord-7dd3edde476e4fbbaea2f70c6118a036
Source dataset
uspto-grants-2013_05
Patent number
US08450313B2

Reaction notes

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