2-Fluoro-3-methylbutyric acid → 1-Phenethylamine

HRID 1929308Notes

Reaction equation

HRID 1929308 reaction equation
[F:1][CH:2]([CH:6]([CH3:8])[CH3:7])[C:3]([OH:5])=[O:4].[CH3:9][C@@H:10]([NH2:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>C(OCC)(=O)C>[CH3:9][CH:10]([NH2:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[F:1][C@@H:2]([CH:6]([CH3:8])[CH3:7])[C:3]([OH:5])=[O:4]

Participants

5

Reactant 2

HCID 153102-Fluoro-3-methylbutyric acidHCID 6431891-Phenethylamine, (+)-

Product 2

HCID 74081-PhenethylamineHCID 55300611HCID 55300611, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

The 2-fluoro-3-methylbutyric acid (˜235.5 g, 1.96 mol), is taken up in ethyl acetate (2.9 L) and R-(+)-α-methylbenzylamine (237.5 g, 1.96 mol) is added dropwise via an addition funnel. A temperature rise to 40° C. is observed. Upon allowing the solution to cool, a slurry results and is stirred at room temperature for 45 minutes. The slurry is then filtered and the filter cake rinsed with ethyl acetate (300 mL). The wet cake is suspended in ethyl acetate (4.5 L) and heated to reflux. Additional ethyl acetate (450 mL) is added to provide a solution, and then the solution is allowed to stand at room temperature overnight. The resulting slurry is filtered and the filter cake rinsed with ethyl acetate (200 mL). The filter cake is vacuum dried at 40° C. to afford 262.3 g of the (R)-+-α-methylbenzylamine salt of (S)-2-fluoro-3-methylbutyric acid as a powder. The enantiomeric excess of this salt is found to be >94% by chiral capillary electrophoresis analysis for the desired (S) isomer.

Workup

  1. customto 40° C.
  2. temperatureto cool
  3. customa slurry results
  4. filtrationThe slurry is then filtered
  5. washthe filter cake rinsed with ethyl acetate (300 mL)
  6. temperatureheated to reflux
  7. additionAdditional ethyl acetate (450 mL) is added
  8. customto provide a solution
  9. waitto stand at room temperature overnight
  10. filtrationThe resulting slurry is filtered
  11. washthe filter cake rinsed with ethyl acetate (200 mL)
  12. customdried at 40° C.

Sources & evidence

ORD record
ord-4d2b35fbec234acda57c22a052c98281
Source dataset
uspto-grants-2012_05
Patent number
US08188069B2

Reaction notes

Loading…