Sodium Carbonate → Dimiracetam

HRID 446127

Reaktionsgleichung

Reaktionsgleichung von HRID 446127
Cl.[NH2:2][CH2:3][C:4]([NH2:6])=[O:5].C([O-])([O-])=O.[Na+].[Na+].[O:13]=[CH:14][CH2:15][CH2:16][C:17](OCC)=O>O>[CH2:16]1[CH:17]2[NH:6][C:4]([CH2:3][N:2]2[C:14](=[O:13])[CH2:15]1)=[O:5]

Komponenten

5

Edukt 3

HCID 10340Sodium Carbonate2×HCID 82395Ethyl 4-oxobutanoateHCID 2723639Glycinamide hydrochloride

Produkt 1

HCID 65955DimiracetamAusbeute 56,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel3×

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

A solution of 2.56 g (22.7 mmol) of glycinamide hydrochloride (purity 98%) in 200 ml of water is heated to 95° C. and the pH adjusted to 6.6 with Na2CO3 20% w/v in water. Then ethyl 4-oxobutanoate (purity 97%) (7.60 g, 56.6 mmol) are added dropwise during four hours maintaining the temperature at 95° C. and the pH at 6.6 by automated addition (pHstat) of Na2CO3 20% w/v in water. The solution is stirred at 95° C. for 1.5 hours and then concentrated to a small volume under vacuum. The obtained suspension is treated with 50 ml of isopropanol and the solvent is evaporated at atmospheric pressure. This operation is repeated once again. The residue is diluted with 50 ml of isopropanol and the resulting suspension heated to 60° C. and then filtered. The filtrate is concentrated to about 15 ml, cooled to room temperature and stirring continued for about 2 hours. The white precipitate is collected by suction filtration, washed with 4 ml of isopropanol and dried under vacuum at 60° C. for 12 hours, resulting in 1.8 g of crude dimiracetam (12.8 mmol, 55.5%). Recrystallization from isopropanol (10 volumes) affords 1.6 g (50%) of pure dimiracetam (>99.5% as determined from area % HPLC). Melting point: 154° C.

Aufarbeitung

  1. concentrationconcentrated to a small volume under vacuum
  2. additionThe obtained suspension is treated with 50 ml of isopropanol
  3. customthe solvent is evaporated at atmospheric pressure
  4. additionThe residue is diluted with 50 ml of isopropanol
  5. temperaturethe resulting suspension heated to 60° C.
  6. filtrationfiltered
  7. concentrationThe filtrate is concentrated to about 15 ml
  8. temperaturecooled to room temperature
  9. stirringstirring
  10. waitcontinued for about 2 hours
  11. filtrationThe white precipitate is collected by suction filtration
  12. washwashed with 4 ml of isopropanol
  13. customdried under vacuum at 60° C. for 12 hours

Quellen und Nachweise

ORD-Eintrag
ord-ec8e384dc1284a5abf7780fc29fc4e2a
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08476453B2

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