Hydrochloric Acid → 3'-Chloro-3-fluoro-4'-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-5-yl)-propyl]-biphenyl-4-carboxylic acid

HRID 2386814Notes

Reaction equation

HRID 2386814 reaction equation
C[O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([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:7][C:6]=1[F:37])=[O:4].[Li+].[OH-].Cl>C1COCC1>[Cl:36][C:13]1[CH:12]=[C:11]([C:8]2[CH:9]=[CH:10][C:5]([C:3]([OH:4])=[O:2])=[C:6]([F:37])[CH:7]=2)[CH:16]=[CH:15][C:14]=1[CH:17]([CH3:35])[C:18]([OH:34])([C:23]1[CH:24]=[CH:25][C:26]2[O:30][C:29](=[O:31])[N:28]([CH3:32])[C:27]=2[CH:33]=1)[C:19]([F:22])([F:21])[F:20]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 666970783'-Chloro-3-fluoro-4'-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-5-yl)-propyl]-biphenyl-4-carboxylic acid methyl ester

Product 1

HCID 666970133'-Chloro-3-fluoro-4'-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-5-yl)-propyl]-biphenyl-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3′-Chloro-3-fluoro-4′-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-5-yl)-propyl]-biphenyl-4-carboxylic acid methyl ester (435 mg, obtained in Example 117) was dissolved in THF (15 mL) followed by the addition of aqueous LiOH solution (1.0M, 1.21 mL). The mixture was stirred at r.t. for 6 hours. The reaction mixture was poured into ice/water and acified with 1M aqueous HCl to pH 1. The aqueous layer was extracted two 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 97:3:0.5) to give the title compound as a white solid. The residual acetic acid was removed by co-evaporation with toluene (250 mg, 59%). MS (neg. ion, m/e)=522.4 [(M−H)−].

Workup

  1. extractionThe aqueous layer was extracted two 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 97:3:0.5)

Sources & evidence

ORD record
ord-95193d1784ae4fd0b35385c351602449
Source dataset
uspto-grants-2012_09
Patent number
US08268820B2

Reaction notes

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