Hydrochloric Acid → HCID 18793463, Verbindung

HRID 406480Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 406480
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=1.[CH2:14]([N:21]1[CH2:26][CH2:25][C:24](=[O:27])[CH:23]([CH3:28])[CH2:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.Cl.[NH4+].[OH-]>CCCCCC.CCOCC>[CH2:14]([N:21]1[CH2:26][CH2:25][C:24]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)([OH:27])[CH:23]([CH3:28])[CH2:22]1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 99931-Bromo-4-fluorobenzeneHCID 14923Ammonium HydroxideHCID 5609651-Benzyl-3-methyl-4-piperidoneHCID 178418339Butyllithium

Produkt 1

HCID 18793463HCID 18793463, VerbindungAusbeute 84,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3283Diethyl EtherLösungsmittel4×HCID 8058HexaneLösungsmittel

Reaktionsbedingungen

Temperatur
-50 °C

Versuchsvorschrift

To a solution of n-butyllithium (1-2 equivalents, preferably 1.1 equivalents) (1.6 M in hexane, 8.6 ml, 13.76 mmol) in Et2O (10.32 mL) was added a solution of 1-bromo-4-fluorobenzene (2.21 g, 12.63 mmol) in Et2O (5 ml) at about −50° C. After the reaction mixture was stirred at about −50° C. for about 40 min, a solution of 1-benzyl-3-methylpiperidin-4-one (2.00 g, 9.84 mmol) in Et2O (7 mL) was added dropwise. The mixture was allowed to warm up to about −20° C. to 0° C. (preferably −10° C.). 1M hydrochloric acid (20 mL) was added and the organic phase was discarded. Et2O (20 mL) was added to the aqueous solution and aqueous NH4OH was added to the solution until pH>9. The organic layer was separated and the aqueous layer was extracted with DCM (20 mL), The combined organic portions were washed with brine (2×10 mL), dried over MgSO4, filtered, and concentrated in vacuo to give 1-benzyl-4-(4-fluorophenyl)-3-methylpiperidin-4-ol (2.48 g, 84%) as an oil which was used in subsequent reactions without further purification. RP-HPLC (Table 1, Method a) Rt 1.63 min; m/z: (M+H)+ 300.

Aufarbeitung

  1. temperatureto warm up to about −20° C. to 0° C. (preferably −10° C.)
  2. additionwas added to the solution until pH>9
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with DCM (20 mL)
  5. washThe combined organic portions were washed with brine (2×10 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-95345ab315f14d0281bad4e14488c3e8
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08754107B2

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