Hydrochloric Acid → (3R)-2-(4-chloro-2-methylphenyl)-4,4,4-trifluoro-3-methylbutanoic acid

HRID 1476112Notes

Reaction equation

HRID 1476112 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C@@H:14]([CH3:19])[C:15]([F:18])([F:17])[F:16])[C:9]([O:11]CC)=[O:10])=[C:4]([CH3:20])[CH:3]=1.Cl>CO.C1COCC1.O.[OH-].[Na+]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C@@H:14]([CH3:19])[C:15]([F:16])([F:17])[F:18])[C:9]([OH:11])=[O:10])=[C:4]([CH3:20])[CH:3]=1

Participants

7

Reactant 2

HCID 313Hydrochloric AcidHCID 58288191Ethyl(3R)-2-(4-chloro-2-methylphenyl)-4,4,4-trifluoro-3-methylbutanoate

Product 1

HCID 58288205(3R)-2-(4-chloro-2-methylphenyl)-4,4,4-trifluoro-3-methylbutanoic acid

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Procedure

3.10 g (crude, about 10.04 mmol) of ethyl (3R)-2-(4-chloro-2-methylphenyl)-4,4,4-trifluoro-3-methylbutanoate (diastereomer mixture) were dissolved in a mixture of 10 ml of methanol, 10 ml of THF and 5 ml of water, and 8.03 g of 50% strength aqueous sodium hydroxide solution were added at 0° C. The reaction mixture was stirred at RT overnight. The mixture was then acidified with 1 N hydrochloric acid (pH about 2) and extracted three times with ethyl acetate. The combined organic phases were washed with sat. sodium chloride solution, dried over magnesium sulphate and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 50:1 to 4:1). This gave 1.46 g (51.8% of theory) of the target product as a mixture of diastereomers (about 5:1).

Workup

  1. additionwere added at 0° C
  2. extractionextracted three times with ethyl acetate
  3. washThe combined organic phases were washed with sat. sodium chloride solution
  4. dry with materialdried over magnesium sulphate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 50:1 to 4:1)
  7. additionThis gave 1.46 g (51.8% of theory) of the target product as a mixture of diastereomers (about 5:1)

Sources & evidence

ORD record
ord-cce49ecfb94643f0b88de50fa29fdca5
Source dataset
uspto-grants-2015_04
Patent number
US09018414B2

Reaction notes

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