Ethyl formate → HCID 59570678, compound

HRID 1961712Notes

Reaction equation

HRID 1961712 reaction equation
CC1(C)CCCC(C)(C)N1.C([Li])CCC.[Cl:16][C:17]1[CH:22]=[N:21][CH:20]=[C:19]([N:23]2[C:27]([CH3:28])=[CH:26][C:25]([CH3:29])=[N:24]2)[N:18]=1.[CH2:30]([O:32]C=O)[CH3:31]>O1CCCC1>[Cl:16][C:17]1[C:22]([CH:30]=[O:32])=[N:21][CH:20]=[C:19]([N:23]2[C:27]([CH3:28])=[CH:26][C:25]([CH3:29])=[N:24]2)[N:18]=1.[Cl:16][C:17]1[N:18]=[C:19]([N:23]2[C:27]([CH3:28])=[CH:26][C:25]([CH3:29])=[N:24]2)[C:31]([CH:30]=[O:32])=[N:21][CH:22]=1

Participants

7

Reactant 4

HCID 8025Ethyl formateHCID 130352,2,6,6-TetramethylpiperidineHCID 432604332-chloro-6-(3,5-dimethyl-1H-pyrazol-1-yl)pyrazineHCID 178418339Butyllithium

Product 2

HCID 59570664HCID 59570664, compoundYield 3%HCID 59570678HCID 59570678, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

2,2,6,6-Tetramethylpiperidine (20.3 mL, 117 mmol) was added to a solution of n-butyllithium (2.5 M in hexanes, 46 mL, 115 mmol) in dry tetrahydrofuran (1.1 L) at −30° C. The mixture was warmed to room temperature and stirred for 15 minutes. After cooling to −78° C. 2-chloro-6-(3,5-dimethyl-pyrazol-1-yl)-pyrazine (20 g, 96 mmol) in dry tetrahydrofuran (15 mL) was added and the mixture was stirred at −78° C. for 1 h. Ethylformate (12 mL, 143 mmol) was added and the mixture stirred for an additional 2 hours at −78° C. The reaction was quenched with aqueous ammonium chloride, warmed to room temperature and diluted with ethyl acetate. The layers were separated and the aqueous phase was extracted with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulphate, filtrated and evaporated to give the crude product as a yellow solid. The crude products were purified by flash chromatography (ethyl acetate/heptane as eluent) to give 3-chloro-5-(3,5-dimethyl-pyrazol-1-yl)-pyrazine-2-carbaldehyde (2.9 g, 13%) as a yellow solid and 5-chloro-3-(3,5-dimethyl-pyrazol-1-yl)-pyrazine-2-carbaldehyde (700 mg, 3%) as a yellow solid.

Workup

  1. temperatureAfter cooling to −78° C
  2. stirringthe mixture was stirred at −78° C. for 1 h
  3. stirringthe mixture stirred for an additional 2 hours at −78° C
  4. customThe reaction was quenched with aqueous ammonium chloride
  5. temperaturewarmed to room temperature
  6. additiondiluted with ethyl acetate
  7. customThe layers were separated
  8. extractionthe aqueous phase was extracted with ethyl acetate
  9. washThe combined organic layers were washed with brine
  10. dry with materialdried over sodium sulphate
  11. filtrationfiltrated
  12. customevaporated
  13. customto give the crude product as a yellow solid
  14. customThe crude products were purified by flash chromatography (ethyl acetate/heptane as eluent)

Sources & evidence

ORD record
ord-1e812972f7e04d579336cd40f0f2d84c
Source dataset
uspto-grants-2013_04
Patent number
US08415358B2

Reaction notes

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