Diethyl Ether → tert-Butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate

HRID 556862Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 556862
[H-].[Al+3].[Li+].[H-].[H-].[H-].[F:7][C:8]1([C:21](OCC)=[O:22])[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1.CCOCC>C1COCC1.C(Cl)(Cl)Cl>[F:7][C:8]1([CH2:21][OH:22])[CH2:9][CH2:10][N:11]([C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])[CH2:12][CH2:13]1

Komponenten

6

Edukt 3

HCID 3283Diethyl EtherHCID 21226445Aluminium lithium hydrideHCID 21306965Ethyl N-Boc-4-fluoropiperidine-4-carboxylate

Produkt 1

HCID 22248400tert-Butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylateAusbeute 69 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6212ChloroformLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Lithium aluminium hydride (1M in THF) (2.36 mL, 2.361 mmol) was added dropwise to a stirred solution of 1-tert-butyl 4-ethyl 4-fluoropiperidine-1,4-dicarboxylate (325 mg, 1.180 mmol) in THF (5.90 mL) cooled to 0° C. After 10 min ether (15 mL) was added and the reaction was quenched by sequential dropwise addition of water (0.1 mL), 10% NaOH (0.1 mL) and water (0.3 mL). The mixture was stirred at room temperature and the lithium salts that had precipitated were filtered off and washed with fresh ether. The organic filtrates were combined and solvent was removed in vacuo to leave a clear gum. The crude product was taken up in chloroform and loaded onto a 25+M Biotage silica column. Chromatography, eluting with a gradient of EtOAc in hexanes, gave tert-butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate (189 mg, 0.810 mmol, 69%) as a clear gum.

Aufarbeitung

  1. customthe reaction was quenched by sequential dropwise addition of water (0.1 mL), 10% NaOH (0.1 mL) and water (0.3 mL)
  2. customthe lithium salts that had precipitated
  3. filtrationwere filtered off
  4. washwashed with fresh ether
  5. customsolvent was removed in vacuo
  6. customto leave a clear gum
  7. washChromatography, eluting with a gradient of EtOAc in hexanes

Quellen und Nachweise

ORD-Eintrag
ord-496a0de35f784a9dbd8e71d0a48c305b
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08058045B2

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