Lithium Hydroxide → 4-{4-Chloro-3-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-2-methoxy-benzoic acid

HRID 1095953Notes

Reaction equation

HRID 1095953 reaction equation
C[O:2][C:3](=[O:35])[C:4]1[CH:9]=[CH:8][C:7]([O:10][C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([CH:18]([CH3:32])[C:19]([C:25]3[CH:30]=[CH:29][N:28]=[C:27]([Cl:31])[CH:26]=3)([OH:24])[C:20]([F:23])([F:22])[F:21])[CH:12]=2)=[CH:6][C:5]=1[O:33][CH3:34].[Li+].[OH-]>C1COCC1.CO>[Cl:17][C:14]1[CH:15]=[CH:16][C:11]([O:10][C:7]2[CH:8]=[CH:9][C:4]([C:3]([OH:35])=[O:2])=[C:5]([O:33][CH3:34])[CH:6]=2)=[CH:12][C:13]=1[CH:18]([CH3:32])[C:19]([C:25]1[CH:30]=[CH:29][N:28]=[C:27]([Cl:31])[CH:26]=1)([OH:24])[C:20]([F:23])([F:21])[F:22]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 595087194-{4-Chloro-3-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-2-methoxy-benzoic acid methyl ester

Product 1

HCID 595086744-{4-Chloro-3-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-2-methoxy-benzoic acid

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

4-{4-Chloro-3-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-2-methoxy-benzoic acid methyl ester (23 mg, obtained in Example 130, step 8) was dissolved in THF/methanol=5/1 (2.5 mL) followed by the addition of aqueous LiOH solution (1.0M, 0.074 mL). The mixture was stirred overnight at r.t. and then 1 hour at 50° C. The reaction mixture was cooled and evaporated. The residue was poured into water and extracted with ethyl acetate. The aqueous phase was acidified with 2 M aqueous HCl to pH 1 and extracted three times with CH2Cl2. The combined organic layers were washed with brine, dried over Na2SO4 and the solvent was evaporated. The title compound was obtained as a colorless solid (14 mg, 63%) and was used without further purification. MS (neg. ion, m/e)=514.1 [(M−H)−].

Workup

  1. custom1 hour
  2. customat 50° C
  3. temperatureThe reaction mixture was cooled
  4. customevaporated
  5. additionThe residue was poured into water
  6. extractionextracted with ethyl acetate
  7. extractionextracted three times with CH2Cl2
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over Na2SO4
  10. customthe solvent was evaporated

Sources & evidence

ORD record
ord-e939de50774844c39952f9da3b1d1122
Source dataset
uspto-grants-2012_03
Patent number
US08138189B2

Reaction notes

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