Hydrochloric Acid → 4-Benzyloxy-2,2-difluorobutylamine

HRID 2072885Notes

Reaction equation

HRID 2072885 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][C:11]([F:25])([F:24])[CH2:12][N:13]1C(=O)C2=CC=CC=C2C1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.NN.Cl>C(O)C>[CH2:1]([O:8][CH2:9][CH2:10][C:11]([F:24])([F:25])[CH2:12][NH2:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 24654Hydrazine hydrate (1:1)HCID 19860700N-(4-benzyloxy-2,2-difluorobutyl)phthalimide

Product 1

HCID 198606944-Benzyloxy-2,2-difluorobutylamine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
5 °C

Procedure

The compound N-(4-benzyloxy-2,2-difluorobutyl)phthalimide (8.97 g, 26 mM) and a 1M solution of hydrazine hydrate in ethanol (26 mL) are stirred under reflux. After a few minutes, a heavy precipitate is observed. Stirring and heating (bath temperature: 90°-100° C.) are continued overnight. Ethanol (220 mL) and concentrated HCl (18 mL) are added, and the mixture is refluxed for an additional 11/2 hour. After cooling (ice) the phthaloyl hydrazide is filtered, and the filtrate is evaporated. The residue is dissolved in water, filtered, and the solution is again evaporated. Residual water is removed by stripping with ethanol (twice) and CCl4 (twice). The residue is dissolved in a minimum amount of ethanol. Crystallization occurs upon the addition of water, which after chilling to 5° C. yields white crystals of 4-benzyloxy-2,2-difluorobutylamine as the hydrochloride salt: 5.16 g (79%).

Workup

  1. temperatureunder reflux
  2. waitAfter a few minutes
  3. temperatureheating (bath temperature: 90°-100° C.)
  4. temperaturethe mixture is refluxed for an additional 11/2 hour
  5. filtrationis filtered
  6. customthe filtrate is evaporated
  7. dissolutionThe residue is dissolved in water
  8. filtrationfiltered
  9. customthe solution is again evaporated
  10. customResidual water is removed
  11. dissolutionThe residue is dissolved in a minimum amount of ethanol
  12. customCrystallization
  13. additionoccurs upon the addition of water, which

Sources & evidence

ORD record
ord-ab06f35455c04fd2b75c7942bd3f4a65
Source dataset
uspto-grants-1990_04
Patent number
US04914240

Reaction notes

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