Isopropanol → 2-Chloro-6-[(propan-2-yl)oxy]pyrazine

HRID 634279Notes

Reaction equation

HRID 634279 reaction equation
[CH3:1][CH:2]([OH:4])[CH3:3].[H-].[Na+].[Cl:7][C:8]1[CH:13]=[N:12][CH:11]=[C:10](Cl)[N:9]=1>C1COCC1>[Cl:7][C:8]1[CH:13]=[N:12][CH:11]=[C:10]([O:4][CH:2]([CH3:3])[CH3:1])[N:9]=1

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 24758Sodium hydrideHCID 785042,6-Dichloropyrazine

Product 1

HCID 246891122-Chloro-6-[(propan-2-yl)oxy]pyrazineYield 86.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-propanol (2.26 mL, 31.99 mmol) in dry THF (40 mL) was added 60% NaH (960 mg, 39.90 mmol) at 0° C. and the reaction was stirred for 15 min. To the mixture at 0° C. was added 2,6-dichloropyrazine (4 g, 26.66 mmol, Aldrich) and the reaction was stirred for 2 h at RT. The reaction was quenched with ice cold H2O (20 mL) and extracted with EtOAc. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified with silica gel column chromatography (eluent: 100% petroleum ether) to afford 2-chloro-6-isopropoxypyrazine (4.0 g, 86%) as an off brown liquid. MS (ESI, pos. ion) m/z: 173.0 (M+1); 1H NMR (400 MHz, CDCl3): δ 8.28 (s, 1H), 8.14 (s, 1H), 5.31-5.25 (m, 1H), 1.37-1.36 (m, 6H).

Workup

  1. stirringthe reaction was stirred for 2 h at RT
  2. customThe reaction was quenched with ice cold H2O (20 mL)
  3. extractionextracted with EtOAc
  4. dry with materialThe organic layer was dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified with silica gel column chromatography (eluent: 100% petroleum ether)

Sources & evidence

ORD record
ord-725246455299469fa8a19cbbb1b058e6
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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