Hydrochloric Acid → HCID 12113038, compound

HRID 989464Notes

Reaction equation

HRID 989464 reaction equation
[CH3:1][C:2]([C:4]1[CH:9]=[CH:8][C:7]([Cl:10])=[CH:6][CH:5]=1)=[O:3].C1([C@@H](N)C)C=CC=CC=1.[CH:20]([C:22]([F:25])([F:24])[F:23])=[O:21].Cl>[Cl-].[Zn+2].[Cl-].C1(C)C=CC=CC=1>[F:23][C:22]([F:25])([F:24])[C@H:20]([OH:21])[CH2:1][C:2]([C:4]1[CH:9]=[CH:8][C:7]([Cl:10])=[CH:6][CH:5]=1)=[O:3]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7467P-ChloroacetophenoneHCID 65564TrifluoroacetaldehydeHCID 758181-Phenethylamine, (-)-

Product 1

HCID 12113038HCID 12113038, compoundYield 98.9%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 1140TolueneSolvent

Conditions

Temperature
25.5 °C

Procedure

At first, 5.5 g (40 mmol) of zinc chloride were added to a toluene solution (4 liters) containing 649 g (4.2 mol) of 4-chloroacetophenone (1b) as a ketone and 484 g (4.0 mol) of (S)-1-phenylethylamine ((S)-2a) as an optically active primary amine, followed by heating under reflux for 20 hr and by removing water (formed as a by-product) with a Dean-Stark tube during the reaction, in order to conduct the reaction. Then, 564 g (4.0 mol) of fluoral.ethylhemiacetal (4a) were dropped to the reaction liquid by spending 80 minutes at a temperature of not higher than 5° C., followed by stirring at 25-26° C. for 24 hr, thereby conducting the reaction. Then, 4-liter of 1N HCl were added to the reaction liquid, followed by stirring at room temperature for 1 hr, then washing with 2-liter of water, then concentration, and then vacuum drying, thereby obtaining 999 g of (R)-4,4,4-trifluoro-3-hydroxy-1-(4-chlorophenyl)-1-butanone ((R)-5ba, purity: 72%). Its optical purity was found to be 54% ee by the chiral HPLC as that of Example 1-30

Workup

  1. temperatureby heating
  2. temperatureunder reflux for 20 hr
  3. customby removing water (
  4. customformed as a by-product) with a Dean-Stark tube
  5. customduring the reaction
  6. customthe reaction
  7. customhigher than 5° C.
  8. customthe reaction
  9. stirringby stirring at room temperature for 1 hr
  10. washwashing with 2-liter of water
  11. concentrationconcentration
  12. customvacuum drying

Sources & evidence

ORD record
ord-898fd2188bf742bda080001b5d702058
Source dataset
uspto-grants-2003_10
Patent number
US06639100B2

Reaction notes

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