Potassium Hydroxide → Levetiracetam

HRID 2309726Notes

Reaction equation

HRID 2309726 reaction equation
[NH2:1][C:2]([C@@H:4]([NH:7][C:8](=[O:13])[CH2:9][CH2:10][CH2:11]Cl)[CH2:5][CH3:6])=[O:3].[OH-].[K+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.ClCCl>[CH2:5]([C@H:4]([N:7]1[CH2:11][CH2:10][CH2:9][C:8]1=[O:13])[C:2]([NH2:1])=[O:3])[CH3:6]

Participants

5

Reactant 2

HCID 14797Potassium Hydroxide2×HCID 29938341N-(1-Amino-1-oxobutan-2-yl)-4-chlorobutanamide, (S)-

Product 1

HCID 5284583LevetiracetamYield 60.7%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6344DichloromethaneSolvent

Procedure

6.2 g (0.03 mole) of (S)-N-[1-(aminocarbonyl)propyl]-4-chlorobutanamide and 0.484 g (0.0015 mole) of tetrabutylammonium bromide are mixed in 45 ml of dichloromethane at 0° C. under a nitrogen atmosphere. 2.02 g (0.036 mole) of potassium hydroxide powder are added over 30 minutes, at such a rate that the temperature of the reaction mixture does not exceed +2° C. The mixture is then stirred for one hour, after which a further 0.1 g (0.0018 mole) of ground potassium hydroxide is added and stirring continued for 30 minutes at 0° C. The mixture is allowed to return to ambient temperature. The insoluble matter is filtered off and the filtrate is concentrated under reduced pressure. The residue obtained is recrystallized from 40 ml of ethyl acetate in the presence of 1.9 g of 0,4 nm molecular sieve. The latter is removed by hot filtration to give 3.10 g of (S)-alpha-ethyl-2-oxo-1-pyrrolidineacetamide.

Workup

  1. customdoes not exceed +2° C
  2. stirringstirring
  3. waitcontinued for 30 minutes at 0° C
  4. customto return to ambient temperature
  5. filtrationThe insoluble matter is filtered off
  6. concentrationthe filtrate is concentrated under reduced pressure
  7. customThe residue obtained
  8. customis recrystallized from 40 ml of ethyl acetate in the presence of 1.9 g of 0,4 nm molecular sieve
  9. customThe latter is removed by hot filtration

Sources & evidence

ORD record
ord-c304cbe51d5e47e3b89ee22a16f3c802
Source dataset
uspto-grants-1987_09
Patent number
US04696943

Reaction notes

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