Chlorosuccinimide → N-(5,6-Dichloropyridin-2-yl)pivalamide

HRID 250085

Reaktionsgleichung

Reaktionsgleichung von HRID 250085
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])[CH:5]=[CH:4][CH:3]=1.[Cl:15]N1C(=O)CCC1=O>C(Cl)(Cl)Cl>[Cl:15][C:3]1[CH:4]=[CH:5][C:6]([NH:8][C:9](=[O:14])[C:10]([CH3:11])([CH3:13])[CH3:12])=[N:7][C:2]=1[Cl:1]

Komponenten

4

Edukt 2

HCID 31398ChlorosuccinimideHCID 13154248N-(6-Chloropyridin-2-yl)-2,2-dimethylpropanamide

Produkt 1

HCID 58088275N-(5,6-Dichloropyridin-2-yl)pivalamideAusbeute 66 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6212ChloroformLösungsmittel

Versuchsvorschrift

To a solution of N-(6-chloropyridin-2-yl)pivalamide, synthesized as in J. Org. Chem 2005, 70, 1771, (1.02 g, 4.80 mmol) in chloroform (25 mL) was added 1-chloropyrrolidine-2,5-dione (0.62 g, 4.67 mmol) and the mixture was refluxed in an oil bath for 3 hrs. It was allowed to cool to room temperature overnight. The reaction mixture was evaporated in vacuo and re-dissolved in DMF (15 mL). Another 480 mg 1-chloropyrrolidine-2,5-dione was added and the resulting solution was heated overnight in an oil bath at 95-100°, then cooled again to room temperature. The solvent was removed in vacuo and the residue was partitioned between water and ethyl acetate. The aqueous phase was washed twice more with ethyl acetate and the combined organic phases were washed with brine, dried over magnesium sulfate, and evaporated in vacuo. TLC (10% ethyl acetate/hexane) showed a robust spot at Rf 0.6 with smaller spots at Rf 0.4 and 0.2. The material was subjected to the Biotage in 5-10% ethyl acetate/hexane, collecting the Rf 0.6 fraction to give 790 mg (66%) white solid, N-(5,6-dichloropyridin-2-yl)pivalamide. 1H NMR (500 MHz, CDCl3) δ ppm 8.17 (s, 1 H), 7.96 (s, 1 H), 7.72 (s, 1 H), 1.31 (s, 10 H). MS (LC/MS) R.T.=1.85; [M+H]+=248.8.

Aufarbeitung

  1. temperaturethe mixture was refluxed in an oil bath for 3 hrs
  2. customThe reaction mixture was evaporated in vacuo
  3. dissolutionre-dissolved in DMF (15 mL)
  4. additionAnother 480 mg 1-chloropyrrolidine-2,5-dione was added
  5. temperaturethe resulting solution was heated overnight in an oil bath at 95-100°
  6. temperaturecooled again to room temperature
  7. customThe solvent was removed in vacuo
  8. customthe residue was partitioned between water and ethyl acetate
  9. washThe aqueous phase was washed twice more with ethyl acetate
  10. washthe combined organic phases were washed with brine
  11. dry with materialdried over magnesium sulfate
  12. customevaporated in vacuo
  13. customcollecting the Rf 0.6 fraction

Quellen und Nachweise

ORD-Eintrag
ord-60c100b0788942ea980359b2e0dd17d7
Quelldatensatz
uspto-grants-2011_01
Patentnummer
US07863291B2

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