Cesium carbonate → 2-[5-(3-Amino-5-methylphenyl)-1,3-thiazol-2-yl]-1-{[tert-butyl(dimethyl)silyl]oxy}propan-2-ol

HRID 410450Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 410450
[CH3:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7](B2OC(C)(C)C(C)(C)O2)[CH:8]=1)[NH2:5].Br[C:19]1[S:23][C:22]([C:24]([OH:35])([CH3:34])[CH2:25][O:26][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28])=[N:21][CH:20]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[Cs+].[Cs+]>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]>[NH2:5][C:4]1[CH:6]=[C:7]([C:19]2[S:23][C:22]([C:24]([OH:35])([CH3:34])[CH2:25][O:26][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28])=[N:21][CH:20]=2)[CH:8]=[C:2]([CH3:1])[CH:3]=1

Komponenten

6

Edukt 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 672361713-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 674313722-(5-Bromo-1,3-thiazol-2-yl)-1-{[tert-butyl(dimethyl)silyl]oxy}propan-2-ol

Produkt 1

HCID 584563302-[5-(3-Amino-5-methylphenyl)-1,3-thiazol-2-yl]-1-{[tert-butyl(dimethyl)silyl]oxy}propan-2-olAusbeute 73,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysator

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (69 mg, 0.296 mmol), the product of Step 2 (104 mg, 0.296 mmol), X-Phos (14.11 mg, 0.030 mmol), cesium carbonate (289 mg, 0.888 mmol), and Pd2(dba)3 (13.55 mg, 0.015 mmol) were placed in a flask flushed with Ar. Degassed Dioxane (1.2 ml) and Water (0.12 ml) were added and heated to 110° C. for 5.5 h. The reaction was allowed to cool to room temperature and then quenched with saturated aqueous sodium bicarbonate and extracted with EtOAc (3×). The combined organics were dried over Na2SO4, filtered and concentrated in vacuo. Purification via silica gel column chromatography (10-30% EtOAc:hexanes) afforded 2-[5-(3-amino-5-methylphenyl)-1,3-thiazol-2-yl]-1-{[tert-butyl(dimethyl)silyl]oxy}propan-2-ol (82 mg, 73%) as a brown oil. MS ESI: [M+H]+ m/z 379.

Aufarbeitung

  1. customflushed with Ar
  2. additionDegassed Dioxane (1.2 ml) and Water (0.12 ml) were added
  3. temperatureto cool to room temperature
  4. customquenched with saturated aqueous sodium bicarbonate
  5. extractionextracted with EtOAc (3×)
  6. dry with materialThe combined organics were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification via silica gel column chromatography (10-30% EtOAc:hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-d1bfed50b5f6490abd03b9c53c9f60b7
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08759366B2

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