Hydrazine hydrate (1:1) → Nebracetam

HRID 1165877Notes

Reaction equation

HRID 1165877 reaction equation
C1(=O)[N:5]([CH2:6][CH:7]2[CH2:11][N:10]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:9](=[O:19])[CH2:8]2)C(=O)C2=CC=CC=C12.O.NN.C(O)(=O)/C=C/C(O)=O>C(O)C>[CH2:12]([N:10]1[CH2:11][CH:7]([CH2:6][NH2:5])[CH2:8][C:9]1=[O:19])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

5

Reactant 3

HCID 24654Hydrazine hydrate (1:1)HCID 444972Fumaric AcidHCID 13504016HCID 13504016, compound

Product 1

HCID 65926Nebracetam

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

54 g (0.16 mol) of 4-phthalimidomethyl-1-benzyl-pyrrolidin-2-one are stirred into 1.3 liters of ethyl alcohol after the addition of 32 g of hydrazine hydrate for 4 hours at ambient temperature. The precipitate (phthalic acid hydrazide) is suction filtered and the filtrate is concentrated by evaporation. 500 ml of methylene chloride are added to the residue and it is extracted three times with 100 ml of water. The organic phase is dried and evaporated. The residue remaining is dissolved in 500 ml of methanol and 20 g (0.17 mol) of solid fumaric acid are added in batches at boiling temperature with stirring. When the mixture cools, colourless crystals are precipitated which are suction filtered and then washed with methanol and ether. Yield: 20-25 g (48-60% of theory), m.p. 209°-211° C.

Workup

  1. filtrationThe precipitate (phthalic acid hydrazide) is suction filtered
  2. concentrationthe filtrate is concentrated by evaporation
  3. addition500 ml of methylene chloride are added to the residue and it
  4. extractionis extracted three times with 100 ml of water
  5. customThe organic phase is dried
  6. customevaporated
  7. dissolutionThe residue remaining is dissolved in 500 ml of methanol
  8. customcolourless crystals are precipitated which
  9. filtrationfiltered
  10. washwashed with methanol and ether

Sources & evidence

ORD record
ord-66014d886de541c9b22043a57df97ac7
Source dataset
uspto-grants-1990_03
Patent number
US04912129

Reaction notes

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