Water → HCID 57415378, Verbindung

HRID 68368

Reaktionsgleichung

Reaktionsgleichung von HRID 68368
C(OC([N:8]([C:12]1[S:13][CH2:14][C@@H:15]2[C@@H:20]([CH3:21])[O:19][CH2:18][C@:16]2([C:22]2[CH:27]=[C:26](Br)[CH:25]=[CH:24][C:23]=2[F:29])[N:17]=1)C([O-])=O)=O)(C)(C)C.O.[F:31][C:32]([F:43])([F:42])[C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[N:37][CH:38]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.C([O-])(O)=O.[Na+].Cl[Pd]Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(O)C>[F:29][C:23]1[CH:24]=[CH:25][C:26]([C:35]2[CH:36]=[N:37][CH:38]=[C:33]([C:32]([F:43])([F:42])[F:31])[CH:34]=2)=[CH:27][C:22]=1[C@:16]12[CH2:18][O:19][C@H:20]([CH3:21])[C@H:15]1[CH2:14][S:13][C:12]([NH2:8])=[N:17]2

Komponenten

9

Edukt 4

HCID 962WaterHCID 10796Cesium carbonateHCID 45158900[5-(Trifluoromethyl)pyridin-3-yl]boronic acidHCID 86707808tert-Butyl[(4aS,5R,7aS)-7a-(5-bromo-2-fluorophenyl)-5-methyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl]imidodicarbonate

Produkt 1

HCID 57415378HCID 57415378, VerbindungAusbeute 25 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 13169693Triphenylphosphine palladium dichlorideKatalysatorHCID 702EthanolLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

tert-Butyl[(4aS,5R,7aS)-7a-(5-bromo-2-fluorophenyl)-5-methyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl]imidodicarbonate (0.15 g, 0.34 mmol) was dissolved in 1,2-dimethoxyethane (1.5 mL), water (0.7 mL) and ethanol (0.5 mL). The resulting solution was heated to 100° C. and to it was added [5-(trifluoromethyl)pyridin-3-yl]boronic acid (0.32 g, 1.68 mmol), cesium carbonate (0.659 g, 2.02 mmol) and dichloropalladium-triphenylphosphane (0.047 g, 0.067 mmol) and the reaction was stirred at 100° C. After 1 hour, the reaction mixture was cooled to room temperature, diluted with saturated aqueous NaHCO3 and extracted with EtOAc (×3). The combined organic layers were dried (MgSO4), filtered and concentrated in vacuo. The residue was purified using column chromatography (gradient 0-60% EtOAc in hexane). The purified product was dissolved in DCM (2 mL) and trifluoroacetic acid (2 L). After 1 hour, the solvents were removed in vacuo. The residue was neutralised with saturated aqueous NaHCO3 and extracted with DCM (×2). The combined organic layers were dried (MgSO4), filtered and concentrated to give the title compound (35 mg, colourless solid).

Aufarbeitung

  1. temperaturethe reaction mixture was cooled to room temperature
  2. extractionextracted with EtOAc (×3)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified
  7. dissolutionThe purified product was dissolved in DCM (2 mL)
  8. waitAfter 1 hour
  9. customthe solvents were removed in vacuo
  10. extractionextracted with DCM (×2)
  11. dry with materialThe combined organic layers were dried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-9ce01cdf0d4646c2ad86ada256a3921f
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822455B2

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