Hydrochloric Acid → 2-[5-(2,4-Dichloro-phenyl)-2-methyl-6-(4-trifluoromethyl-phenyl)-pyridin-3-ylmethoxy]-2-methyl-propionic acid

HRID 526689Notes

Reaction equation

HRID 526689 reaction equation
C([O:3][C:4](=[O:35])[C:5]([O:8][CH2:9][C:10]1[C:11]([CH3:34])=[N:12][C:13]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=2)=[C:14]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=2[Cl:23])[CH:15]=1)([CH3:7])[CH3:6])C.[Li+].[OH-].Cl>C1COCC1.O>[Cl:23][C:17]1[CH:18]=[C:19]([Cl:22])[CH:20]=[CH:21][C:16]=1[C:14]1[CH:15]=[C:10]([CH2:9][O:8][C:5]([CH3:7])([CH3:6])[C:4]([OH:35])=[O:3])[C:11]([CH3:34])=[N:12][C:13]=1[C:24]1[CH:25]=[CH:26][C:27]([C:30]([F:32])([F:33])[F:31])=[CH:28][CH:29]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 899073012-[5-(2,4-Dichloro-phenyl)-2-methyl-6-(4-trifluoromethyl-phenyl)-pyridin-3-ylmethoxy]-2-methyl-propionic acid ethyl ester

Product 1

HCID 725444642-[5-(2,4-Dichloro-phenyl)-2-methyl-6-(4-trifluoromethyl-phenyl)-pyridin-3-ylmethoxy]-2-methyl-propionic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 200 mg of 2-[5-(2,4-Dichloro-phenyl)-2-methyl-6-(4-trifluoromethyl-phenyl)-pyridin-3-ylmethoxy]-2-methyl-propionic acid ethyl ester in 2 ml THF was added a solution of 18 mg of LiOH in 2 ml water at room temperature. After 16 h, the mixture was brought to pH 2 by addition of 1 M hydrochloric acid. The reaction mixture was concentrated under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic phases were dried over MgSO4 and the solvents were removed under reduced pressure. The residue was purified by preparative HPLC (C18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to yield a white solid. Yield: 22 mg.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. extractionthe aqueous layer was extracted with dichloromethane
  3. dry with materialThe combined organic phases were dried over MgSO4
  4. customthe solvents were removed under reduced pressure
  5. customThe residue was purified by preparative HPLC (
  6. washC18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA)
  7. additionThe fractions containing the product
  8. customwere evaporated
  9. customto yield a white solid

Sources & evidence

ORD record
ord-ffebc8ca8d434bb6b895b6613e37b165
Source dataset
uspto-grants-2016_05
Patent number
US09346757B2

Reaction notes

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