Cesium carbonate → 7-bromo-1-fluoro-3-(neopentyloxy)-5H-chromeno[2,3-c]pyridin-5-one

HRID 455699Notes

Reaction equation

HRID 455699 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5](F)=[C:6]([C:8]([C:10]2[CH:15]=[C:14]([O:16][CH2:17][C:18]([CH3:21])([CH3:20])[CH3:19])[N:13]=[C:12]([F:22])[C:11]=2[O:23]COC)=[O:9])[CH:7]=1.B(Br)(Br)Br.[Cl-].[NH4+].C(=O)([O-])[O-].[Cs+].[Cs+]>C(Cl)Cl.C(#N)C.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]([O:16][CH2:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:15][C:10]=1[C:8]2=[O:9]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 25134Boron tribromideHCID 25517Ammonium ChlorideHCID 67383169(5-Bromo-2-fluorophenyl)(2-fluoro-3-(methoxymethoxy)-6-(neopentyloxy)pyridin-4-yl)methanone

Product 1

HCID 673828597-bromo-1-fluoro-3-(neopentyloxy)-5H-chromeno[2,3-c]pyridin-5-oneYield 78.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of (5-bromo-2-fluorophenyl)(2-fluoro-3-(methoxymethoxy)-6-(neopentyloxy)pyridin-4-yl)methanone (1.89 g, 4.25 mmol) in DCM (20 mL) was cooled to −78° C. under nitrogen atmosphere. Boron tribromide (1.0M in CH2Cl2; 4.25 mL, 4.25 mmol) was added drop wise and the reaction mixture was stirred for 5 min at rt. Aqueous, saturated ammonium chloride solution was added, followed by water and DCM. The organic phase was separated and dried over magnesium sulfate. The solvent was removed under reduced pressure to afford a yellow solid, which was dissolved in ACN (20.00 mL). Cesium carbonate (1.386 g, 4.25 mmol) was added in one portion and the reaction mixture was allowed to stir for 5 min. Water was added and the remaining light-yellow solid was filtered off and dried to afford 7-bromo-1-fluoro-3-(neopentyloxy)-5H-chromeno[2,3-c]pyridin-5-one (1.27 g).

Workup

  1. customThe organic phase was separated
  2. dry with materialdried over magnesium sulfate
  3. customThe solvent was removed under reduced pressure
  4. customto afford a yellow solid, which
  5. stirringto stir for 5 min
  6. filtrationthe remaining light-yellow solid was filtered off
  7. customdried

Sources & evidence

ORD record
ord-00c5125f7aa044e5b708969161754882
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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