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 ethyl ester

HRID 2386893Notes

Reaction equation

HRID 2386893 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[CH:9]([CH3:27])[C:10]([C:16]1[CH:17]=[CH:18][C:19]2[O:23][C:22](=[O:24])[N:21]([CH3:25])[C:20]=2[CH:26]=1)([OH:15])[C:11]([F:14])([F:13])[F:12].Br[C:29]([CH3:36])([CH3:35])[C:30]([O:32][CH2:33][CH3:34])=[O:31].[OH-].[Na+].Cl>CC(N(C)C)=O.O>[CH2:33]([O:32][C:30](=[O:31])[C:29]([O:8][C:6]1[CH:5]=[CH:4][C:3]([CH:9]([CH3:27])[C:10]([OH:15])([C:16]2[CH:17]=[CH:18][C:19]3[O:23][C:22](=[O:24])[N:21]([CH3:25])[C:20]=3[CH:26]=2)[C:11]([F:12])([F:13])[F:14])=[C:2]([Cl:1])[CH:7]=1)([CH3:36])[CH3:35])[CH3:34]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11745Propanoic acid, 2-bromo-2-methyl-, ethyl esterHCID 14798Sodium HydroxideHCID 666969865-[2-(2-Chloro-4-hydroxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-3-methyl-3H-benzooxazol-2-one

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

5-[2-(2-Chloro-4-hydroxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-3-methyl-3H-benzooxazol-2-one (80 mg, obtained in Example 172) and ethyl 2-bromoisobutyrate (0.2 mL) were dissolved in dimethylacetamide (2 mL). Powdered sodium hydroxide (54 mg) was added to this solution and the mixture was allowed to stir at r.t. for 12 hours. The mixture was poured into water and ice and was acidified to pH 3 with 2N HCl. The aqueous phase was extracted with ethyl acetate two times and the organic extracts were washed with brine, dried over Na2SO4 and evaporated in vacuo. The residue was purified by flash chromatography (silica gel, ethyl acetate:hexanes=4:1) 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 ethyl ester as a colorless foam (113 mg). MS (m/e, ISP neg. ion)=514.1 [M−H+].

Workup

  1. extractionThe aqueous phase was extracted with ethyl acetate two times
  2. washthe organic extracts were washed with brine
  3. dry with materialdried over Na2SO4
  4. customevaporated in vacuo
  5. customThe residue was purified by flash chromatography (silica gel, ethyl acetate:hexanes=4:1)

Sources & evidence

ORD record
ord-0613333e9fba451294b07b3c55b1b43f
Source dataset
uspto-grants-2012_09
Patent number
US08268820B2

Reaction notes

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