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

HRID 1427144Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1427144
Br[C:2]1[CH:3]=[CH:4][C:5]([C:23]([F:26])([F:25])[F:24])=[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:27]([Si:31]([CH3:40])([CH3:39])[O:32][CH:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1)([CH3:30])([CH3:29])[CH3:28].C([O-])([O-])=O.[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>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:31]([O:32][CH:33]1[CH2:34][CH2:35][N:36]([C:2]2[CH:3]=[CH:4][C:5]([C:23]([F:26])([F:25])[F:24])=[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])[CH2:37][CH2:38]1)([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:40])[CH3:39]

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 114813284-((Tert-butyldimethylsilyl)oxy)piperidineHCID 86707378Methyl 4-[[5-bromo-2-(trifluoromethyl)benzoyl]amino]-3,5-dimethyl-benzoate

Produkt 1

HCID 86707379Methyl 4-[[5-[4-[tert-butyl(dimethyl)silyl]oxy-1-piperidyl]-2-(trifluoromethyl)benzoyl]amino]-3,5-dimethyl-benzoateAusbeute 80 %

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a solution of methyl 4-[[5-bromo-2-(trifluoromethyl)benzoyl]amino]-3,5-dimethyl-benzoate (0.10 g, 232.44 μmol), tert-butyl-dimethyl-(4-piperidyloxy)silane (55.08 mg, 255.68 mmol, see preparation 3) and Cs2CO3 (227.2 mg, 697.32 μmol) in 1,4-dioxane (2.5 ml) is added Pd2(dba)3 (21.28 mg, 23.24 μmol) followed by 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (S-Phos) (9.54 mg, 23.24 μmol). The reaction mixture is purged with nitrogen for 5 minutes and then heated at 120° C. After 8 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 (neutral alumina) using of 15%-85% ethyl acetate in hexanes as eluent to afford the title compound as a pale yellow oil (0.10 g, 80%). Mass spectrum (m/z): 565.4 (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 (neutral alumina)

Quellen und Nachweise

ORD-Eintrag
ord-4200485ac6c8485785a6cc2ab698d16c
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08933098B2

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