Sodium hydride → 2-chloro-3-(tetrahydro-2H-pyran-4-yloxy)pyrazine
Reaction equation
[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH:6]([OH:9])[CH2:5][CH2:4]1.[Cl:10][C:11]1[C:16](Cl)=[N:15][CH:14]=[CH:13][N:12]=1>C1COCC1>[Cl:10][C:11]1[C:16]([O:9][CH:6]2[CH2:7][CH2:8][O:3][CH2:4][CH2:5]2)=[N:15][CH:14]=[CH:13][N:12]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
Sodium hydride (60% dispersion in mineral oil, 0.22 g, 5.39 mmol) was added to a solution of tetrahydro-4H-pyran-4-ol (0.47 mL, 4.90 mmol) in THF (10 mL) and the mixture was stirred for 30 mins, during which time a suspension formed. This mixture was added dropwise to a solution of 2,3-dichloropyrazine (0.73 g, 4.90 mmol) in THF (10 mL) at −78° C. under argon. The cooling bath was removed and the mixture was stirred for 3 h with warming to RT. Ethyl acetate and saturated aqueous ammonium chloride were added, the layers were separated, and the organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to give an oil that was purified by silica gel chromatography to give 2-chloro-3-(tetrahydro-2H-pyran-4-yloxy)pyrazine (0.75 g, 3.49 mmol, 71% yield) as a white solid.
Workup
- customformed
- customThe cooling bath was removed
- stirringthe mixture was stirred for 3 h
- additionEthyl acetate and saturated aqueous ammonium chloride were added
- customthe layers were separated
- dry with materialthe organic layer was dried over anhydrous magnesium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
- customto give an oil that
- customwas purified by silica gel chromatography
Sources & evidence
- ORD record
- ord-b62cdbbebcf14496aaff4bbb52aa56bc
- Source dataset
- uspto-grants-2015_02
- Patent number
- US08946230B2
Reaction notes
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