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

HRID 2386859Notes

Reaction equation

HRID 2386859 reaction equation
C[O:2][C:3](=[O:38])[C:4]1[CH:9]=[CH:8][C:7]([O:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]([CH3:35])[C:18]([OH:34])([C:23]3[CH:24]=[CH:25][C:26]4[O:30][C:29](=[O:31])[N:28]([CH3:32])[C:27]=4[CH:33]=3)[C:19]([F:22])([F:21])[F:20])=[C:13]([Cl:36])[CH:12]=2)=[CH:6][C:5]=1[Cl:37].[Li+].[OH-].Cl>C1COCC1>[Cl:37][C:5]1[CH:6]=[C:7]([O:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]([CH3:35])[C:18]([OH:34])([C:23]3[CH:24]=[CH:25][C:26]4[O:30][C:29](=[O:31])[N:28]([CH3:32])[C:27]=4[CH:33]=3)[C:19]([F:22])([F:21])[F:20])=[C:13]([Cl:36])[CH:12]=2)[CH:8]=[CH:9][C:4]=1[C:3]([OH:38])=[O:2]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 666971192-Chloro-4-{3-chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-5-yl)-propyl]-phenoxy}-benzoic acid methyl ester

Product 1

HCID 666970322-Chloro-4-{3-chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-5-yl)-propyl]-phenoxy}-benzoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-Chloro-4-{3-chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-5-yl)-propyl]-phenoxy}-benzoic acid methyl ester (33 mg, obtained in Example 173, step 1) was dissolved in THF (2 mL) followed by the addition of aqueous LiOH solution (1.0M, 0.14 mL). The mixture was stirred for 5 hours at r.t. The reaction mixture was poured into ice/water and acified with 1M aqueous HCl to pH 1. The aqueous layer was extracted three times with ethylacetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and the solvent was evaporated. The residue was purified by flash chromatography (silica gel, CH2Cl2:MeOH:CH3COOH=100:0:0 to 98:2:0.5) to give the title compound as a light yellow foam. The residual acetic acid was removed by co-evaporation with toluene (10 mg, 31%). MS (neg. ion, m/e)=554.3 [(M−H)−].

Workup

  1. extractionThe aqueous layer was extracted three times with ethylacetate
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customthe solvent was evaporated
  6. customThe residue was purified by flash chromatography (silica gel, CH2Cl2:MeOH:CH3COOH=100:0:0 to 98:2:0.5)

Sources & evidence

ORD record
ord-6c27ab5087cc4a188b975f03210b84ea
Source dataset
uspto-grants-2012_09
Patent number
US08268820B2

Reaction notes

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