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

HRID 455569Notes

Reaction equation

HRID 455569 reaction equation
[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

Participants

9

Reactant 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

Product 1

HCID 67382973(5-amino-7-bromo-3-chloro-8-fluoro-5H-chromeno[2,3-b]pyridin-5-yl)methanolYield 25.9%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

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).

Workup

  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]

Sources & evidence

ORD record
ord-c23527199c87403b80fd160b5b6657b6
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

Loading…