Lithium diisopropylamide → HCID 178455347, Verbindung

HRID 2235305Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2235305
[C:1]([Si:5]([CH3:21])([CH3:20])[O:6][C@H:7]1[CH2:12][CH2:11][C@H:10]([N:13]2[CH2:18][CH2:17][CH2:16][CH2:15][C:14]2=[O:19])[CH2:9][CH2:8]1)([CH3:4])([CH3:3])[CH3:2].[Li+].CC([N-]C(C)C)C.Br[CH2:31][C:32]1[C:37]([F:38])=[CH:36][CH:35]=[CH:34][C:33]=1[Cl:39]>C1COCC1>[Cl:39][C:33]1[CH:34]=[CH:35][CH:36]=[C:37]([F:38])[C:32]=1[CH2:31][CH:15]1[CH2:16][CH2:17][CH2:18][N:13]([C@H:10]2[CH2:9][CH2:8][C@H:7]([O:6][Si:5]([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:21])[CH3:20])[CH2:12][CH2:11]2)[C:14]1=[O:19]

Komponenten

5

Edukt 3

HCID 2724682Lithium diisopropylamideHCID 27736252-Chloro-6-fluorobenzyl bromideHCID 178455338HCID 178455338, Verbindung

Produkt 1

HCID 178455347HCID 178455347, VerbindungAusbeute 45,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

Dissolve trans-1-(4-[tert-butyl-dimethyl-silanyloxy)-cyclohexyl]-piperidin-2-one (0.3 g, 0.96 mmol) in anhydrous THF (6 mL) under nitrogen, cool to −78° C. and add LDA (2M solution in THF) (0.72 mL, 1.44 mmol) dropwise. Stir the reaction mixture for 5 minutes and add 2-bromomethyl-1-chloro-3-fluoro-benzene (0.3 g, 1.44 mmol) in anhydrous THF (2 mL) dropwise. Stir the reaction mixture at −78° C. for 3 hours, slowly warm to room temperature, quench with saturated aqueous NH4Cl (5 mL) and extract with DCM (3×10 mL). Dry the organic layer over Na2SO4, remove the solvent and purify the residue by chromatography over silica gel (eluting with 0 to 20% EtOAc in hexane) to obtain trans-3-(-2-chloro-6-fluoro-benzyl)-1-(4-[tert-butyl-dimethyl-silanyloxy]-cyclohexyl)-piperidin-2-one as a white solid (0.2 g). Dissolve the trans-3-(-2-chloro-6-fluoro-benzyl)-1-(4-[tert-butyl-dimethyl-silanyloxy]-cyclohexyl)-piperedin-2-one in methanol containing concentrated hydrochloric acid (5% v/v) and heat at 40° C. for 1 hour. Evaporate the solvent, dissolve the residue in DCM (10 mL) and wash with saturated aqueous NaHCO3 (5 mL). Dry the organic layer over anhydrous Na2SO4, remove the solvent and purify the residue by chromatography over silica gel (eluting with 0 to 50% EtOAc in hexane) to obtain the title compound as a clear oil (110 mg, 34%): MS (ES+) m/z=340 (M+H)+.

Aufarbeitung

  1. stirringStir the reaction mixture at −78° C. for 3 hours
  2. temperatureslowly warm to room temperature
  3. customquench with saturated aqueous NH4Cl (5 mL)
  4. extractionextract with DCM (3×10 mL)
  5. dry with materialDry the organic layer over Na2SO4
  6. customremove the solvent
  7. custompurify the residue by chromatography over silica gel (eluting with 0 to 20% EtOAc in hexane)

Quellen und Nachweise

ORD-Eintrag
ord-7cde30b03a9041c99355267b86097f13
Quelldatensatz
uspto-grants-2010_05
Patentnummer
US07713979B2

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