Hydrochloric Acid → 1-Benzyloxy-2,2-difluorobutylamine

HRID 2309591Notes

Reaction equation

HRID 2309591 reaction equation
[CH2:1]([O:8][CH2:9][C:10]([F:25])([F:24])[CH2:11][CH2:12]N1C(=O)C2=CC=CC=C2C1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.NN.Cl.C(NN)(=O)C1C(=CC=CC=1)C([NH:35]N)=O>C(O)C>[CH2:1]([O:8][CH:9]([NH2:35])[C:10]([F:25])([F:24])[CH2:11][CH3:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24654Hydrazine hydrate (1:1)HCID 11367556PhthalohydrazideHCID 13935581N-(4-benzyloxy-3,3-difluorobutyl)phthalimide

Product 1

HCID 545334691-Benzyloxy-2,2-difluorobutylamine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent3×

Procedure

The compound N-(4-benzyloxy-3,3-difluorobutyl)phthalimide (68.5 g, 198.6 mmoles) and hydrazine hydrate (10 g, 200 mmoles) are stirred and heated overnight in ethanol (200 mL) at 90°-100° C. A mixture of concentrated HCl (94 mL) and ethanol (1130 mL) is added, and heating (90°-100° C.) is continued for 1.5 hours. After cooling (ice bath), phthalhydrazide is removed by filtration, and the filtrate is evaporated. The residue is taken up in water and extracted with ether (2×500 mL). After filtration through a membrane filter (Millipore), evaporation of the filtrate yields white crystals. These dissolved in ethanol, the solution is filtered (Millipore organic) and the filtrate is evaporated to yield a residue which crystallizes on addition of ether: 34 g (68%). Evaporation of the ether extracts yields a partially crystalline material (20 g) consisting of starting material. Repetition of the hydrazine cleavage upon this mixture yields a second crop of 4-benzyloxy-3,3-difluorobutylamine (9.1 g). Total: 43.2 g (86.5%).

Workup

  1. additionis added
  2. temperatureheating (90°-100° C.)
  3. customis removed by filtration
  4. customthe filtrate is evaporated
  5. extractionextracted with ether (2×500 mL)
  6. filtrationAfter filtration through a membrane
  7. filtrationfilter
  8. custom(Millipore), evaporation of the filtrate
  9. customyields white crystals
  10. filtrationthe solution is filtered (Millipore organic)
  11. customthe filtrate is evaporated
  12. customto yield a residue which
  13. customcrystallizes on addition of ether
  14. customEvaporation of the ether

Sources & evidence

ORD record
ord-16ad6af7876e41df9e7a50fdb23f1525
Source dataset
uspto-grants-1987_09
Patent number
US04695654

Reaction notes

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