Potassium Hydroxide → Etiracetam, (R)-

HRID 2309708Notes

Reaction equation

HRID 2309708 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.C(Cl)(Cl)(Cl)Cl>[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

6

Reactant 2

HCID 14797Potassium HydroxideHCID 54219251(R)-N-[1-(aminocarbonyl)propyl]-4-chlorobutanamide

Product 1

HCID 441341Etiracetam, (R)-Yield 75.4%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 5943Carbon TetrachlorideSolventHCID 6344DichloromethaneSolvent

Procedure

6.2 g (0.03 mole) of (R)-N-[1-(aminocarbonyl)propyl]-4-chlorobutanamide and 0.484 g (0.0015 mole) of tetrabutylammonium bromide are mixed in 42 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 stirred for 15 minutes and then allowed to return to ambient temperature. The insoluble material is filtered off and the filtrate concentrated under reduced pressure. The residue obtained is stirred in 25 ml of carbon tetrachloride for 30 minutes, and then filtered off and dried. The product is recrystallized in 45 ml of ethyl acetate in the presence of 1.7 g of 0,4 nm molecular sieve. The latter is removed by hot filtration to give 3.85 g of (R)-alpha-ethyl-2-oxo-1-pyrrolidineacetamide. Melting point: 116°-118° C. [alpha]D25 : +89.8° (c=1, acetone). Yield: 75.4%.

Workup

  1. customdoes not exceed +2° C
  2. customto return to ambient temperature
  3. filtrationThe insoluble material is filtered off
  4. concentrationthe filtrate concentrated under reduced pressure
  5. customThe residue obtained
  6. filtrationfiltered off
  7. customdried
  8. customThe product is recrystallized in 45 ml of ethyl acetate in the presence of 1.7 g of 0,4 nm molecular sieve
  9. customThe latter is removed by hot filtration

Sources & evidence

ORD record
ord-3fd83e61c13f4760b7e68d81b0067fbc
Source dataset
uspto-grants-1987_09
Patent number
US04696942

Reaction notes

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