Sodium bis(trimethylsilyl)amide → (R)-2-(3,4-Difluorophenyl)-4-[3-(tert-butyldimethylsiloxy)-1-butoxy]-5-bromo-3(2H)-pyridazinone

HRID 1241869Notes

Reaction equation

HRID 1241869 reaction equation
[O:1]([C@H:9]([CH3:13])[CH2:10][CH2:11][OH:12])[Si:2]([C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:4])[CH3:3].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[F:24][C:25]1[CH:26]=[C:27]([N:32]2[C:37](=[O:38])[C:36](Br)=[C:35]([Br:40])[CH:34]=[N:33]2)[CH:28]=[CH:29][C:30]=1[F:31]>C1COCC1>[F:24][C:25]1[CH:26]=[C:27]([N:32]2[C:37](=[O:38])[C:36]([O:12][CH2:11][CH2:10][C@H:9]([O:1][Si:2]([C:5]([CH3:6])([CH3:7])[CH3:8])([CH3:4])[CH3:3])[CH3:13])=[C:35]([Br:40])[CH:34]=[N:33]2)[CH:28]=[CH:29][C:30]=1[F:31]

Participants

5

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 110527501-Butanol, 3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-, (3R)-HCID 159418894,5-Dibromo-2-(3,4-difluorophenyl)pyridazin-3(2H)-one

Product 1

HCID 23598336(R)-2-(3,4-Difluorophenyl)-4-[3-(tert-butyldimethylsiloxy)-1-butoxy]-5-bromo-3(2H)-pyridazinoneYield 51.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred, 0° C. solution of the product from Example 545B (3.4 g, 10 mmol) in THF (20 mL) was added 1M sodium bis(trimethylsilyl)amide in THF (12 mL, 12 mmol). The reaction mixture was stirred at room temperature for 0.5 hours, then it was transferred to a stirred, −30° C. solution of 2-(3,4-difluorophenyl)-4,5-dibromo-3(2H)-pyridazinone (3.66 g, 10 mmol) in THF (100 mL). The reaction mixture was stirred at −30° C. for 1 hour, then overnight while warming to room temperature. The reaction was quenched with saturated aqueous ammonium chloride solution (100 mL) and extracted with ethyl acetate (2×100 mL). The organic layer was washed with brine (2×20 mL), then dried (MgSO4), and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (silica gel, 90:10 hexane/ethyl acetate) to provide the title intermediate (2.5 g, 51%).

Workup

  1. stirringThe reaction mixture was stirred at −30° C. for 1 hour
  2. temperatureovernight while warming to room temperature
  3. customThe reaction was quenched with saturated aqueous ammonium chloride solution (100 mL)
  4. extractionextracted with ethyl acetate (2×100 mL)
  5. washThe organic layer was washed with brine (2×20 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customthe residue was purified by column chromatography (silica gel, 90:10 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-80b0e8f5ecf44292a60fb8169b8bc01e
Source dataset
uspto-grants-2006_10
Patent number
US07115591B2

Reaction notes

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