Cesium carbonate → 2-Bromo-6-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-benzaldehyde

HRID 2069855Notes

Reaction equation

HRID 2069855 reaction equation
Br[C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([Br:10])[C:3]=1[CH:4]=[O:5].[C:11]([C:15]1[CH:16]=[C:17]2[C:22](=[C:23]([F:25])[CH:24]=1)[C:21](=[O:26])[NH:20][N:19]=[CH:18]2)([CH3:14])([CH3:13])[CH3:12].C(=O)([O-])[O-].[Cs+].[Cs+].COC1C2C(=C3C(=CC=2)C(OC)=CC=N3)N=CC=1>[Cu]I.O1CCOCC1>[Br:10][C:6]1[CH:7]=[CH:8][CH:9]=[C:2]([N:20]2[N:19]=[CH:18][C:17]3[C:22](=[C:23]([F:25])[CH:24]=[C:15]([C:11]([CH3:12])([CH3:14])[CH3:13])[CH:16]=3)[C:21]2=[O:26])[C:3]=1[CH:4]=[O:5]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 104622984,7-Dimethoxy-1,10-phenanthrolineHCID 126486412,6-DibromobenzaldehydeHCID 594737656-(tert-Butyl)-8-fluorophthalazin-1(2H)-one

Product 1

HCID 594737882-Bromo-6-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-benzaldehydeYield 43.8%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

1518 mg (5.75 mmol) of 2,6-dibromobenzaldehyde, 506 mg (2.30 mmol) of 6-tert-butyl-8-fluoro-2H-phthalazin-1-one, 1499 mg (4.60 mmol) of cesium carbonate, 42 mg (0.22 mmol) of copper(I) iodide, and 115 mg (0.479 mmol) of 4,7-dimethoxy-1,10-phenanthroline were weighed into a 20 mL reaction vial fitted with a stir bar and septum cap. Added 8 mL of anhydrous dioxane. Purged the reaction mixture with nitrogen for 15 min. Stirred at 100° C. for 16 h. Partitioned the reaction mixture between 25 ml, of 10% MeOH/CH2Cl2 and 25 mL of water. Separated phases and extracted the aqueous phase with 25 mL of 10% MeOH/CH2Cl2. Filtered to break the stable emulsion. The combined organic extracts were washed with 75 mL of brine, dried over MgSO4, and the solvent was removed on rotavap. Purified by silica gel flash chromatography using gradient elution with 0→40% EtOAc/hexane to obtain 406 mg of the title compound as a yellow solid. MS (ESI) doublet 403, 405 (M+H)+.

Workup

  1. customvial fitted with a stir bar
  2. customseptum cap
  3. customPurged the reaction mixture with nitrogen for 15 min
  4. customPartitioned the reaction mixture between 25 ml
  5. extractionSeparated phases and extracted the aqueous phase with 25 mL of 10% MeOH/CH2Cl2
  6. filtrationFiltered
  7. washThe combined organic extracts were washed with 75 mL of brine
  8. dry with materialdried over MgSO4
  9. customthe solvent was removed on rotavap
  10. customPurified by silica gel flash chromatography
  11. washelution with 0→40% EtOAc/hexane

Sources & evidence

ORD record
ord-dcaa603a7f644d048f2926e9cedb0baf
Source dataset
uspto-grants-2012_10
Patent number
US08299077B2

Reaction notes

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