Boron tribromide → HCID 67383094, compound

HRID 335956Notes

Reaction equation

HRID 335956 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5](F)=[C:6]([CH:8]([C:10]2[CH:15]=[C:14]([CH:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[N:13]=[C:12]([F:22])[C:11]=2[O:23]COC)[OH:9])[CH:7]=1.C[N+]1([O-])CCOCC1.[Cl-].[NH4+].B(Br)(Br)Br.C(=O)(O)[O-].[Na+]>C(Cl)Cl.[Ru]([O-])(=O)(=O)=O.C([N+](CCC)(CCC)CCC)CC.O>[Br:1][C:2]1[CH:7]=[C:6]2[C:5](=[CH:4][CH:3]=1)[O:23][C:11]1[C:12]([F:22])=[N:13][C:14]([CH:16]3[CH2:17][CH2:18][O:19][CH2:20][CH2:21]3)=[CH:15][C:10]=1[C:8]2=[O:9]

Participants

9

Reactant 5

HCID 25134Boron tribromideHCID 25517Ammonium ChlorideHCID 82029Methyl morpholine oxideHCID 516892Sodium BicarbonateHCID 67383208HCID 67383208, compound

Product 1

HCID 67383094HCID 67383094, compoundYield 90%

Reagents, catalysts & solvents 3

HCID 178419074HCID 178419074, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

(5-Bromo-2-fluorophenyl)(2-fluoro-3-(methoxymethoxy)-6-(tetrahydro-2H-pyran-4-yl)pyridin-4-yl)methanol (0.84 g, 1.90 mmol) was dissolved in DCM (30 mL) and treated with 4-methylmorpholine 4-oxide (0.56 g, 4.74 mmol). Once the reagent had dissolved tetrapropylammonium perruthenate (0.033 g, 0.095 mmol) was added and the pale yellow solution stirred at RT. After 10 min the mixture had turned dark. Additional DCM (50 mL) was added followed by water (50 mL) and saturated ammonium chloride (50 mL). The phases were mixed and separated and the organic dried with magnesium sulfate before evaporating to dryness under reduced pressure. The crude was redissolved in dichloromethane (25 mL) and cooled in an ice bath under nitrogen. Boron tribromide (neat, 0.25 mL, 2.64 mmol) was added and the mixture turned orange yellow. After 10 min saturated sodium bicarbonate (70 mL) and DCM (100 mL) were added. The phases were mixed and separated and the organic dried with magnesium sulfate before evaporating to dryness under reduced pressure. The crude was treated with excess cesium carbonate (1.2 g) and ACN (50 mL) and stirred at room temperature for 10 min. The mixture was evaporated to dryness under reduced pressure. The crude product was partitioned between DCM (100 mL) and water (100 mL). The organic was dried with magnesium sulfate and evaporated to dryness under reduced pressure to give 7-bromo-1-fluoro-3-(tetrahydro-2H-pyran-4-yl)-5H-chromeno[2,3-c]pyridin-5-one (0.645 g, 1.705 mmol, 90% yield) as a white solid. It was used without purification.

Workup

  1. additionwas added
  2. additionThe phases were mixed
  3. customseparated
  4. dry with materialthe organic dried with magnesium sulfate
  5. custombefore evaporating to dryness under reduced pressure
  6. dissolutionThe crude was redissolved in dichloromethane (25 mL)
  7. temperaturecooled in an ice bath under nitrogen
  8. additionThe phases were mixed
  9. customseparated
  10. dry with materialthe organic dried with magnesium sulfate
  11. custombefore evaporating to dryness under reduced pressure
  12. additionThe crude was treated with excess cesium carbonate (1.2 g) and ACN (50 mL)
  13. stirringstirred at room temperature for 10 min
  14. customThe mixture was evaporated to dryness under reduced pressure
  15. customThe crude product was partitioned between DCM (100 mL) and water (100 mL)
  16. dry with materialThe organic was dried with magnesium sulfate
  17. customevaporated to dryness under reduced pressure

Sources & evidence

ORD record
ord-f97251be4b134ff68d17e5551dbd5ade
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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