Sodium sulfate decahydrate → (5-amino-7-bromo-3-chloro-8-fluoro-5H-chromeno[2,3-b]pyridin-5-yl)methanol

HRID 931560Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 931560
[Br:1][C:2]1[CH:3]=[C:4]2[C:14](=[CH:15][C:16]=1[F:17])[O:13][C:7]1=[N:8][CH:9]=[C:10]([Cl:12])[CH:11]=[C:6]1[C:5]2=O.[I-].C[S+](C)C.C[C:25](C)([O-:27])C.[K+].C[Si]([N:34]=[N+]=[N-])(C)C.[H-].[H-].[H-].[H-].[Li+].[Al+3].O.O.O.O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Na+].[Na+]>CS(C)=O.CCOC(C)=O>[NH2:34][C:5]1([CH2:25][OH:27])[C:6]2[C:7](=[N:8][CH:9]=[C:10]([Cl:12])[CH:11]=2)[O:13][C:14]2[C:4]1=[CH:3][C:2]([Br:1])=[C:16]([F:17])[CH:15]=2

Komponenten

9

Edukt 6

HCID 62649Sodium sulfate decahydrateHCID 75127Trimethylsulfonium iodideHCID 78378AzidotrimethylsilaneHCID 21226445Aluminium lithium hydrideHCID 23665647Potassium tert-butoxideHCID 574756457-bromo-3-chloro-8-fluoro-5H-chromeno[2,3-b]pyridin-5-one

Produkt 1

HCID 67382973(5-amino-7-bromo-3-chloro-8-fluoro-5H-chromeno[2,3-b]pyridin-5-yl)methanolAusbeute 25,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A solution of 7-bromo-3-chloro-8-fluoro-5H-chromeno[2,3-b]pyridin-5-one (10.00 g, 30.4 mmol) and trimethylsulfonium iodide (6.83 g, 33.5 mmol) in 150 mL DMSO under argon atmosphere was treated with potassium tert-butoxide (3.76 g, 33.5 mmol) at rt. After 75 minutes, trimethylsilylazide (8.08 mL, 60.9 mmol) was added, and the reaction mixture was allowed to stir overnight. The reaction mixture was then diluted with EtOAc and washed with water. The suspension was filtered, and the filtrate was dried over MgSO4 and concentrated under reduced pressure. The crude residue was taken up in 100 mL THF and cooled to 0° C. LAH (1.155 g, 30.4 mmol) was added, and the reaction mixture was allowed to stir for 30 minutes. The ice bath was removed, and the reaction mixture was allowed to stir for an additional 30 minutes. The reaction mixture was then cooled back to 0° C. and quenched with sodium sulfate decahydrate (9.81 g, 30.4 mmol). After stirring for one hour, the reaction mixture was filtered through celite and concentrated under reduced pressure. Purification of the crude residue by column chromatography [0-80% (95:5 EtOAc/MeOH)/DCM] gave (5-amino-7-bromo-3-chloro-8-fluoro-5H-chromeno[2,3-b]pyridin-5-yl)methanol (2.83 g, 7.87 mmol, 25.9% yield).

Aufarbeitung

  1. washwashed with water
  2. filtrationThe suspension was filtered
  3. dry with materialthe filtrate was dried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. stirringto stir for 30 minutes
  6. customThe ice bath was removed
  7. stirringto stir for an additional 30 minutes
  8. temperatureThe reaction mixture was then cooled back to 0° C.
  9. stirringAfter stirring for one hour
  10. filtrationthe reaction mixture was filtered through celite and
  11. concentrationconcentrated under reduced pressure
  12. customPurification of the crude residue by column chromatography [0-80% (95:5 EtOAc/MeOH)/DCM]

Quellen und Nachweise

ORD-Eintrag
ord-364e93fea39a45ae8133719d7998ddbf
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09296759B2

Notizen zur Reaktion

Wird geladen…