Dimethylformamide → 3-(tert-Butoxy)pyrazine-2-carbaldehyde

HRID 914800Notes

Reaction equation

HRID 914800 reaction equation
CC1(C)CCCC(C)(C)N1.C([Li])CCC.[C:16]([O:20][C:21]1[CH:26]=[N:25][CH:24]=[CH:23][N:22]=1)([CH3:19])([CH3:18])[CH3:17].CN(C)[CH:29]=[O:30]>O1CCCC1.C(OCC)(=O)C.O>[C:16]([O:20][C:21]1[C:26]([CH:29]=[O:30])=[N:25][CH:24]=[CH:23][N:22]=1)([CH3:19])([CH3:17])[CH3:18]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 130352,2,6,6-TetramethylpiperidineHCID 132568902-Tert-butoxypyrazineHCID 178418339Butyllithium

Product 1

HCID 222482803-(tert-Butoxy)pyrazine-2-carbaldehydeYield 45%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-50 °C

Procedure

After dissolving 2.50 ml of 2,2,6,6-tetramethylpiperidine in 40 ml of tetrahydrofuran, the solution was cooled to −50° C. Next, 5.25 ml of n-butyllithium (2.6 M, n-hexane solution) was added dropwise thereto under a nitrogen atmosphere. The mixture was stirred for 25 minutes, cooled on ice, and stirred for an additional 35 minutes. It was then cooled to −78° C., and a solution of 1.89 g of 2-tert-butoxypyrazine [CAS No. 70090-30-1] in tetrahydrofuran (5 ml) was added dropwise. After stirring the mixture for 15 minutes, 1.25 ml of N, N-dimethylformamide was added dropwise. After 10 minutes, water was added to the reaction solution and extraction was performed with ethyl acetate. The organic layer was washed with water and saturated brine in that order and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate) to obtain the title compound (1.00 g, 45% yield).

Workup

  1. temperaturecooled on ice
  2. stirringstirred for an additional 35 minutes
  3. temperatureIt was then cooled to −78° C.
  4. stirringAfter stirring the mixture for 15 minutes
  5. waitAfter 10 minutes
  6. washThe organic layer was washed with water and saturated brine in that order
  7. dry with materialdried over anhydrous magnesium sulfate
  8. distillationthe solvent was distilled off under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-f2285fb9056a4b11bc4b779ba72b006c
Source dataset
uspto-grants-2007_09
Patent number
US07265108B2

Reaction notes

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