Chloroacetyl chloride → tert-Butyl 3-oxo-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

HRID 1689220Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1689220
Cl[CH2:2][C:3](Cl)=[O:4].C(=O)([O-])[O-].[K+].[K+].[NH2:12][CH2:13][C:14]1([OH:27])[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1>O.C(OCC)(=O)C>[O:4]=[C:3]1[NH:12][CH2:13][C:14]2([CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:24])([CH3:26])[CH3:25])=[O:21])[CH2:18][CH2:19]2)[O:27][CH2:2]1

Komponenten

6

Edukt 3

HCID 6577Chloroacetyl chlorideHCID 11430Potassium CarbonateHCID 23396319tert-Butyl 4-(aminomethyl)-4-hydroxypiperidine-1-carboxylate

Produkt 1

HCID 57989097tert-Butyl 3-oxo-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Chloroacetyl chloride (4.88 mL) was added dropwise to a vigorously stirred mixture at 0° C. of potassium carbonate (17.43 g) in water (78 mL) and tert-butyl 4-(aminomethyl)-4-hydroxypiperidine-1-carboxylate (10.4 g) in ethyl acetate (92 mL). After 30 minutes at 0° C. the mixture was extracted with ethyl acetate and the organic layer dried over sodium sulfate, filtered and the solvent evaporated under reduced pressure. The residue was dissolved in THF (200 mL) and added dropwise over 3 hours to a stirred solution under nitrogen and heated at reflux of potassium tert-butoxide (1M in tert-butanol, 75 mL) and THF (250 mL). The mixture was cooled to room temperature and allowed to stir for 18 hours. Most of the solvent was removed under reduced pressure and the residue partitioned between ethyl acetate and brine, the aqueous layer was re-extracted with ethyl acetate and the combined organics were dried over sodium sulfate, filtered and the solvent removed under reduced pressure. The residue was purified by trituration with a mixture of ether (30 mL) and isohexane (20 mL) to afford the subtitled product. Yield 8.20 g.

Aufarbeitung

  1. extractionAfter 30 minutes at 0° C. the mixture was extracted with ethyl acetate
  2. dry with materialthe organic layer dried over sodium sulfate
  3. filtrationfiltered
  4. customthe solvent evaporated under reduced pressure
  5. dissolutionThe residue was dissolved in THF (200 mL)
  6. additionadded dropwise over 3 hours to a stirred solution under nitrogen
  7. temperatureheated
  8. temperatureat reflux of potassium tert-butoxide (1M in tert-butanol, 75 mL) and THF (250 mL)
  9. customMost of the solvent was removed under reduced pressure
  10. customthe residue partitioned between ethyl acetate and brine
  11. extractionthe aqueous layer was re-extracted with ethyl acetate
  12. dry with materialthe combined organics were dried over sodium sulfate
  13. filtrationfiltered
  14. customthe solvent removed under reduced pressure
  15. customThe residue was purified by trituration with a mixture of ether (30 mL) and isohexane (20 mL)

Quellen und Nachweise

ORD-Eintrag
ord-42d98f89c81d43b1836de5d99da7c815
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08148373B2

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