tert-Butyl 4-oxopiperidine-1-carboxylate → Tert-butyl 4-(3-bromobenzylidene)piperidine-1-carboxylate

HRID 657395

Reaktionsgleichung

Reaktionsgleichung von HRID 657395
C(OP([CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([Br:16])[CH:11]=1)(=O)OCC)C.O=[C:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]1.CC(C)([O-])C.[K+]>O1CCCC1>[Br:16][C:12]1[CH:11]=[C:10]([CH:9]=[C:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)[CH:15]=[CH:14][CH:13]=1

Komponenten

5

Edukt 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 10979718Diethyl 3-BromobenzylphosphonateHCID 23665647Potassium tert-butoxide2×

Produkt 1

HCID 57813409Tert-butyl 4-(3-bromobenzylidene)piperidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To diethyl[(3-bromophenyl)methyl]phosphonate (100 g, 326 mmol) in a 2 L 3-neck flask with mechanical stirrer was added tetrahydrofuran (THF) (700 mL) followed by 1,1-dimethylethyl 4-oxo-1-piperidinecarboxylate (71.4 g, 358 mmol) and potassium tert-butoxide (38.4 g, 342 mmol), portion-wise with ice-bath cooling to keep the temperature between 20° C. and 25° C. The mixture became more orange and was then stirred at room temperature under nitrogen. Some material was present as a suspension and it was slightly more viscous. Another 3.8 g (0.1 eq) of potassium tert-butoxide was added. After 1.25 h the mixture had practically gelled: an extra 150 mL of THF were added. The mixture was partitioned between water and ethyl acetate and the aqueous layer extracted well with ethyl acetate. The combined organics were washed with water, brine, dried (MgSO4), filtered and evaporated to give a pale yellow oil, 120.73 g. The crude product was purified on a 750 g Companion XL silica cartridge, eluting with 0-25% ethyl acetate in cyclohexane over 8 column volumes. This gave a colorless oil which became a white solid, 94.68 g (83%). HPLC 2.97 min (ret time), 99.5%; LC-MS m/z 352,354 (M+H)+, 3.96 min (ret time).

Aufarbeitung

  1. temperaturecooling
  2. customthe temperature between 20° C. and 25° C
  3. customThe mixture was partitioned between water and ethyl acetate
  4. extractionthe aqueous layer extracted well with ethyl acetate
  5. washThe combined organics were washed with water, brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customto give a pale yellow oil, 120.73 g
  10. customThe crude product was purified on a 750 g Companion XL silica cartridge
  11. washeluting with 0-25% ethyl acetate in cyclohexane over 8 column volumes
  12. customThis gave a colorless oil which
  13. customHPLC 2.97 min (ret time), 99.5%
  14. customLC-MS m/z 352,354 (M+H)+, 3.96 min (ret time)

Quellen und Nachweise

ORD-Eintrag
ord-c01b1d1e70fb4e84868d0d7701042ba3
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08071588B2

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