Sodium hydride → 1,5-Bis(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one

HRID 2097491Notes

Reaction equation

HRID 2097491 reaction equation
[CH3:1][Si:2]([CH3:18])([CH3:17])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[C:11]2[CH:12]=[N:13][NH:14][C:15](=[O:16])[C:10]=2[CH:9]=[CH:8]1.[H-].[Na+].[CH3:21][Si:22]([CH3:29])([CH3:28])[CH2:23][CH2:24][O:25][CH2:26]Cl.[Cl-].[NH4+]>CN(C)C=O>[CH3:1][Si:2]([CH3:18])([CH3:17])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[C:11]2[CH:12]=[N:13][N:14]([CH2:26][O:25][CH2:24][CH2:23][Si:22]([CH3:29])([CH3:28])[CH3:21])[C:15](=[O:16])[C:10]=2[CH:9]=[CH:8]1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 666030201-(2-Trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one

Product 1

HCID 666029251,5-Bis(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-oneYield 48%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 1.5 L of dehydrated N,N-dimethylformamide solution containing 107 g (0.403 mol) of 1-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one obtained in Reference example 16-(b) was added 22.2 g (0.509 mol) of sodium hydride (55% dispersed material in mineral oil) by dividing it into several portions under argon atmosphere and under ice-cooling, and the mixture was stirred at room temperature for 1 hour. Then, 85.9 g (0.515 mol) of (2-trimethylsilylethoxy)methyl chloride was added dropwise to the mixture under ice-cooling, and the mixture was stirred at room temperature for 5 hours. After completion of the reaction, the reaction mixture was poured into ice-water, neutralized with a saturated aqueous solution of ammonium chloride, and extracted with toluene. The organic layer after separation was washed successively with water and then a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The obtained concentrate was recrystallized from 400 ml of cyclohexane to obtain 76.2 g of the title compound as a white solid. (Yield: 48%)

Workup

  1. temperatureunder ice-cooling
  2. temperaturecooling
  3. stirringthe mixture was stirred at room temperature for 5 hours
  4. customAfter completion of the reaction
  5. extractionextracted with toluene
  6. customThe organic layer after separation
  7. washwas washed successively with water
  8. dry with materiala saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. concentrationThe obtained concentrate
  11. customwas recrystallized from 400 ml of cyclohexane

Sources & evidence

ORD record
ord-6063a3a87d47444f801f1fe9dd507f7b
Source dataset
uspto-grants-2013_05
Patent number
US08450319B2

Reaction notes

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