Cesium carbonate → Methyl 4-[[5-[3-[[tert-butyl(dimethyl)silyl]oxymethyl]-1-piperidyl]-2-fluoro-benzoyl]amino]-3,5-dimethyl-benzoate

HRID 239925Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 239925
Br[C:2]1[CH:3]=[CH:4][C:5]([F:23])=[C:6]([CH:22]=1)[C:7]([NH:9][C:10]1[C:19]([CH3:20])=[CH:18][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][C:11]=1[CH3:21])=[O:8].[C:24]([Si:28]([CH3:38])([CH3:37])[O:29][CH2:30][CH:31]1[CH2:36][CH2:35][CH2:34][NH:33][CH2:32]1)([CH3:27])([CH3:26])[CH3:25].C([O-])([O-])=O.[Cs+].[Cs+].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Si:28]([O:29][CH2:30][CH:31]1[CH2:36][CH2:35][CH2:34][N:33]([C:2]2[CH:3]=[CH:4][C:5]([F:23])=[C:6]([CH:22]=2)[C:7]([NH:9][C:10]2[C:19]([CH3:20])=[CH:18][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][C:11]=2[CH3:21])=[O:8])[CH2:32]1)([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:38])[CH3:37]

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 58992622Tert-butyl-dimethyl-(3-piperidylmethoxy)silaneHCID 86707311Methyl 4-[(5-bromo-2-fluoro-benzoyl)amino]-3,5-dimethyl-benzoate

Produkt 1

HCID 86707312Methyl 4-[[5-[3-[[tert-butyl(dimethyl)silyl]oxymethyl]-1-piperidyl]-2-fluoro-benzoyl]amino]-3,5-dimethyl-benzoateAusbeute 40 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

To a solution of methyl 4-[(5-bromo-2-fluoro-benzoyl)amino]-3,5-dimethyl-benzoate (0.40 g, 1.05 mmol), tert-butyl-dimethyl-(3-piperidylmethoxy)silane (0.362 g, 1.57 mmol) and Cs2CO3 (1.04 g, 3.15 mmol) in 1,4-dioxane (6 ml) is added Pd2(dba)3 (0.10 g, 0.105 mmol) followed by S-Phos (0.043 g, 0.105 mmol). The reaction mixture is purged with nitrogen for 5 minutes and then heated at 90° C. After 16 hours, the reaction is cooled to ambient temperature, filtered through Celite™, and washed with EtOAc. The combined filtrates are dried over sodium sulfate, filtered, and concentrated under reduced pressure and purified by flash chromatography (silica gel) using 10% EtOAc in hexane to afford the title compound as a pale yellow oil (0.22 g, 40%). Mass spectrum (m/z): 529.2 (M+1).

Aufarbeitung

  1. customThe reaction mixture is purged with nitrogen for 5 minutes
  2. temperaturethe reaction is cooled to ambient temperature
  3. filtrationfiltered through Celite™
  4. washwashed with EtOAc
  5. dry with materialThe combined filtrates are dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. custompurified by flash chromatography (silica gel)

Quellen und Nachweise

ORD-Eintrag
ord-90a14014be26474cbfefdc7ded207a64
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08642768B2

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