Pyridine → Benzyl 4-hydroxy-4-(pyridin-3-yl)piperidine-1-carboxylate

HRID 1721798

Reaktionsgleichung

Reaktionsgleichung von HRID 1721798
C([Li])CCC.Br[C:7]1[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=1.N1C=CC=CC=1.[C:19]([N:29]1[CH2:34][CH2:33][C:32](=[O:35])[CH2:31][CH2:30]1)([O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:20]>O1CCCC1>[C:19]([N:29]1[CH2:30][CH2:31][C:32]([C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)([OH:35])[CH2:33][CH2:34]1)([O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:20]

Komponenten

6

Edukt 4

HCID 1049PyridineHCID 122863-BromopyridineHCID 643496Benzyl 4-oxopiperidine-1-carboxylateHCID 178418339Butyllithium

Produkt 1

HCID 21480587Benzyl 4-hydroxy-4-(pyridin-3-yl)piperidine-1-carboxylateAusbeute 75 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a cooled solution (-78° C.) of n-butyllithium (2.0M in hexane, 12.9 mL, 28.3 mmol, 1.2 eq) in tetrahydrofuran (200 mL) under nitrogen was added 3-bromopyridine (2.27 mL, 23.6 mmol, 1.1 eq). The solution became a dark green color as the pyridine was added. The reaction was stirred at this temperature for 1h, at which time 1-carbobenzyloxy-4-piperidone (described in example 87c) (5.00 g, 21.4 mmol) was added as a tetrahydrofuran solution (20 mL). The cooling bath was removed and the reaction warmed to room temperature, stirring at that temperature for 18 h. The reaction was quenched by the addition of water (125 mL) and the aqueous phase extracted with ethyl acetate (3×75 mL). Combined organic extracts were dried over anhydrous magnesium sulfate, filtered, and reduced to an oil. The reaction product was purified by flash chromatography over silica gel (300 mL, eluent: ethyl acetate) to yield 5.00 g (75%) of the title compound as an oil. TLC analysis (Rf 0.10, ethyl acetate). MS (CI, CH4) m/z 313 (M+1,100), 341 (M+29,15), 295 (15).

Aufarbeitung

  1. additionwas added
  2. customThe cooling bath was removed
  3. customThe reaction was quenched by the addition of water (125 mL)
  4. extractionthe aqueous phase extracted with ethyl acetate (3×75 mL)
  5. dry with materialCombined organic extracts were dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customThe reaction product was purified by flash chromatography over silica gel (300 mL, eluent: ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-a80b55c8763e44aa945ed206cdcc9da3
Quelldatensatz
uspto-grants-1996_04
Patentnummer
US05512575

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