Sodium hydride → 1-{4-[({5-[2-Fluoro-3-(hydroxymethyl)phenyl]pyrimidin-2-yl}oxy)methyl]piperidin-1-yl}ethan-1-one

HRID 2171674Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2171674
[OH:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9](=[O:11])[CH3:10])[CH2:5][CH2:4]1.[H-].[Na+].[Si]([O:21][CH2:22][C:23]1[C:24]([F:36])=[C:25]([C:29]2[CH:30]=[N:31][C:32](Cl)=[N:33][CH:34]=2)[CH:26]=[CH:27][CH:28]=1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1>CCOC(C)=O.O.C1COCC1>[F:36][C:24]1[C:23]([CH2:22][OH:21])=[CH:28][CH:27]=[CH:26][C:25]=1[C:29]1[CH:34]=[N:33][C:32]([O:1][CH2:2][CH:3]2[CH2:4][CH2:5][N:6]([C:9](=[O:11])[CH3:10])[CH2:7][CH2:8]2)=[N:31][CH:30]=1

Komponenten

8

Edukt 4

HCID 24758Sodium hydrideHCID 11078149TBAF tetrahydrofuranHCID 189349231-[4-(Hydroxymethyl)piperidin-1-yl]ethan-1-oneHCID 866862315-[3-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]-2-chloropyrimidine

Produkt 1

HCID 683098421-{4-[({5-[2-Fluoro-3-(hydroxymethyl)phenyl]pyrimidin-2-yl}oxy)methyl]piperidin-1-yl}ethan-1-oneAusbeute 82 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

1-[4-(Hydroxymethyl)piperidin-1-yl]ethan-1-one (200 mg) and THF (4 ml) were mixed, and NaH (70 mg) was added thereto, followed by stirring at room temperature for 10 minutes. 5-[3-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]-2-chloropyrimidine (200 mg) was added to the reaction mixture, followed by stirring at room temperature for 1 hour, and then 1M TBAF/THF (1.2 ml) was added thereto, followed by stirring at room temperature. Water and EtOAc were added to the reaction mixture, and the organic layer was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/EtOAc/CHCl3/MeOH) to obtain 1-{4-[({5-[2-fluoro-3-(hydroxymethyl)phenyl]pyrimidin-2-yl}oxy)methyl]piperidin-1-yl}e than-1-one (167 mg).

Aufarbeitung

  1. stirringby stirring at room temperature for 1 hour
  2. stirringby stirring at room temperature
  3. concentrationthe organic layer was concentrated under reduced pressure
  4. customThe obtained residue was purified by silica gel column chromatography (hexane/EtOAc/CHCl3/MeOH)

Quellen und Nachweise

ORD-Eintrag
ord-6e4591bf49544d56a4ad9596b22faad0
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09051283B2

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