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

HRID 1419552Notes

Reaction equation

HRID 1419552 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.[N+](C1C=CC(C(O)C(N(C)C)CO)=CC=1)([O-])=O.COC1C=CC2N=CC=C([C@@H](O)[C@H]3N4C[C@H](C=C)[C@@H](CC4)C3)C=2C=1>CCOCC>[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

5

Reactant 3

HCID 3034034QuinineHCID 44309071-(4-Nitrophenyl)-2-dimethylamino-1,3-propanediolHCID 131185654-(Difluoromethoxy)-alpha-(1-methylethyl)benzeneacetic acid

Product 1

HCID 13118566(S)-2-(4-difluoromethoxyphenyl)-3-methylbutyric acid

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

1 part of 2-(4-difluoromethoxyphenyl)-3-methylbutyric acid is dissolved in 1-5 parts (by weight) of solvent comprising an organic solvent such as an aliphatic alcohol, an aromatic hydrocarbon, a keton, a halogenated hydrocarbon, an ether, an ester, or an aliphatic hydrocarbon, etc. After the dissolution is completed, 1-3 moles of resolving agent, an optically active organic base such as 1-(4-nitrophenyl)-2-dimethylamino-1,3-propanediol, quinine, substituted α-aminoethylbenzene and the like, is added. The mixture thus obtained is stirred at -50° C. to 200° C., preferably at 0° C. to reflux temperature of the solvent, for 0.1-100 hours, preferably for 1-10 hours. After the reaction is completed, the reaction mixture is allowed to cool, the solids are then collected by filtration and the filtrate discarded. The solids were added to an aqueous solution of 0.1%-36%, preferably 5%-20%, hydrochloric acid, and heated with stirring at 0° C.-100° C., preferably at 20° C.-50° C., for 0.2-1 hour. Thereafter, the reaction mixture was allowed to cool to room temperature, extracted with organic solvents such as aromatic hydrocarbons, halogenated hydrocarbons, aliphatic hydrocarbons, ethers, ketones, esters and the like, and then remove the solvent in the extract by distillation to give (S)-2-(4-difluoromethoxyphenyl)-3-methylbutyric acid.

Workup

  1. customThe mixture thus obtained
  2. temperatureto reflux temperature of the solvent
  3. waitpreferably for 1-10 hours
  4. temperatureto cool
  5. filtrationthe solids are then collected by filtration
  6. additionThe solids were added to an aqueous solution of 0.1%-36%, preferably 5%-20%, hydrochloric acid
  7. temperatureheated
  8. stirringwith stirring at 0° C.-100° C., preferably at 20° C.-50° C., for 0.2-1 hour
  9. temperatureto cool to room temperature
  10. extractionextracted with organic solvents such as aromatic hydrocarbons, halogenated hydrocarbons, aliphatic hydrocarbons, ethers, ketones, esters
  11. customthe like, and then remove the solvent in the
  12. extractionextract by distillation

Sources & evidence

ORD record
ord-be24fcada0634676a2e4d6eac98f92ee
Source dataset
uspto-grants-1999_03
Patent number
US05886207

Reaction notes

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