Hydrochloric Acid → Lacosamide EP Impurity E

HCl (8.00 g, 219.4 mmol) was passed into MeOH (250 mL), and then D-serine ((R)-5) (20.00 g, 190.3 mmol) was added. The reaction solution was heated at reflux (18 h), then benzylamine (81.6 mL, 761 mmol) was added, and then the reaction mixture was heated for additional 18 h. The solvent was removed under reduced pressure, the insoluble salts were filtered, and the excess benzylamine was removed under high vacuum (Kugelrohr). The residue was dissolved in H2O (100 mL), and the product was extracted with CHCl3 (8×200 mL). The organic layers were combined and dried (Na2SO4), and the solvent was removed under reduced pressure. The residue was triturated with Et2O (150 mL) and filtered to vie 10.0 g (27%) of the product as white solid: mp 74-78° C.; [α]23D (c=1, MeOH)=1.6°.

1. temperatureThe reaction solution was heated
2. temperatureat reflux (18 h)
3. temperaturethe reaction mixture was heated for additional 18 h
4. customThe solvent was removed under reduced pressure
5. filtrationthe insoluble salts were filtered
6. customthe excess benzylamine was removed under high vacuum (Kugelrohr)
7. dissolutionThe residue was dissolved in H2O (100 mL)
8. extractionthe product was extracted with CHCl3 (8×200 mL)
9. dry with materialdried (Na2SO4)
10. customthe solvent was removed under reduced pressure
11. customThe residue was triturated with Et2O (150 mL)
12. filtrationfiltered
13. custom[α]23D (c=1, MeOH)=1.6°

ORD 기록

ord-d0cbed8867034340a8cd44f6584476a4

출처 데이터셋

uspto-grants-2000_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US06133261