Quinine → (S)-2-(4-difluoromethoxyphenyl)-3-methylbutyric acid

HRID 1419557Notes

Reaction equation

HRID 1419557 reaction equation
[F:1][CH:2]([F:17])[O:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]([CH:14]([CH3:16])[CH3:15])[C:11]([OH:13])=[O:12])=[CH:6][CH:5]=1.COC1C=CC2N=CC=C([C@@H](O)[C@H]3N4C[C@H](C=C)[C@@H](CC4)C3)C=2C=1>C1(C)C=CC=CC=1>[F:1][CH:2]([F:17])[O:3][C:4]1[CH:5]=[CH:6][C:7]([C@H:10]([CH:14]([CH3:15])[CH3:16])[C:11]([OH:13])=[O:12])=[CH:8][CH:9]=1

Participants

4

Reactant 2

HCID 3034034QuinineHCID 131185654-(Difluoromethoxy)-alpha-(1-methylethyl)benzeneacetic acid

Product 1

HCID 13118566(S)-2-(4-difluoromethoxyphenyl)-3-methylbutyric acidYield 42%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Dissolve 50 g of 2-(4-difluoromethoxyphenyl)-3-methylbutyric acid in 130 g of toluene and to this solution is added 0.24 mole of resolving agent quinine. Heat the solution with stirring under reflux for 6 hours, then cool, filter, and transfer the resulting solids to 49 g of 15% hydrochloric acid. Heat the mixture with stirring at 40° C. for 2 hours and then allow the mixture to cool to room temperature. The resulting mixture is extracted with benzene 2-3 times, and the solvent benzene is then removed by distillation to give 21 g (yield: 42%) of (S)-2-(4-difluoromethoxyphenyl)-3-methylbutyric acid. [α]DRT =(+)40.5 (c=1.356 g/100 ml, CHCl2)

Workup

  1. additionto this solution is added 0.24 mole
  2. temperatureHeat the solution
  3. temperatureunder reflux for 6 hours
  4. temperaturecool
  5. filtrationfilter
  6. temperatureHeat the mixture
  7. stirringwith stirring at 40° C. for 2 hours
  8. extractionThe resulting mixture is extracted with benzene 2-3 times
  9. customthe solvent benzene is then removed by distillation

Sources & evidence

ORD record
ord-b7f61f5574d04e3cafb6bbe87a3a4164
Source dataset
uspto-grants-1999_03
Patent number
US05886207

Reaction notes

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