Sodium hydride → 3-Iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole-4-carbonitrile
Reaction equation
[I:1][C:2]1[C:6]([C:7]#[N:8])=[CH:5][NH:4][N:3]=1.[H-].[Na+].Cl[CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17]>O1CCCC1>[I:1][C:2]1[C:6]([C:7]#[N:8])=[CH:5][N:4]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[N:3]=1Participants
Conditions
- Temperature
- 0 °C
Procedure
Into a 100-mL round-bottom flask, was placed a solution of 3-iodo-1H-pyrazole-4-carbonitrile (compound 256.1, 5.00 g, 22.8 mmol) in tetrahydrofuran (10 mL). The solution was cooled to 0° C. under nitrogen, then sodium hydride (1.1 g, 27.4 mmol, 60% dispersion in mineral oil) was added in portions. The resulting mixture was stirred at 0° C. for 30 min, then (2-(chloromethoxy)ethyl)trimethylsilane (6.05 mL, 34.2 mmol) was added to the reaction. The resulting mixture was stirred for overnight at room temperature, then carefully quenched with water/ice (30 mL). The aqueous phase was extracted with ethyl acetate (2×100 mL) and the combined organic layers were dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by a silica gel chromatography with ethyl acetate/petroleum ether (20:1) as eluent to obtain the title compound as a colorless oil (7.2 g, 90%).
Workup
- customInto a 100-mL round-bottom flask, was placed
- stirringThe resulting mixture was stirred for overnight at room temperature
- customcarefully quenched with water/ice (30 mL)
- extractionThe aqueous phase was extracted with ethyl acetate (2×100 mL)
- dry with materialthe combined organic layers were dried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customThe residue was purified by a silica gel chromatography with ethyl acetate/petroleum ether (20:1) as eluent
Sources & evidence
- ORD record
- ord-85090ed7ebf149e8a0befc311e9c5a5e
- Source dataset
- uspto-grants-2016_08
- Patent number
- US09428502B2
Reaction notes
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