2-Methylpiperidine → 2-Chloro-6-(2-methyl-1-piperidinyl)pyrazine

HRID 518050Notes

Reaction equation

HRID 518050 reaction equation
Cl[C:2]1[CH:7]=[N:6][CH:5]=[C:4]([Cl:8])[N:3]=1.[CH3:9][CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][NH:11]1.C(=O)([O-])[O-].[K+].[K+].CC(N(C)C)=O>O>[Cl:8][C:4]1[CH:5]=[N:6][CH:7]=[C:2]([N:11]2[CH2:12][CH2:13][CH2:14][CH2:15][CH:10]2[CH3:9])[N:3]=1

Participants

6

Reactant 4

HCID 79742-MethylpiperidineHCID 11430Potassium CarbonateHCID 31374DimethylacetamideHCID 785042,6-Dichloropyrazine

Product 1

HCID 534091142-Chloro-6-(2-methyl-1-piperidinyl)pyrazineYield 87%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2,6-dichloropyrazine (1.49 g), 2-methylpiperidine (1.76 mL), potassium carbonate (2.07 g) and DMA (10 mL) was stirred at 80° C. for 22 hr. Water (10 mL) was added, and the mixture was extracted with ethyl acetate. The aqueous layer was extracted again with ethyl acetate. The combined organic layer was washed with water and saturated brine, dried over magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (solvent gradient: 5→20% ethyl acetate/hexane) to give the title compound (1.85 g, 87%) as a pale-yellow oil.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. extractionThe aqueous layer was extracted again with ethyl acetate
  3. washThe combined organic layer was washed with water and saturated brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography (solvent gradient: 5→20% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-9990e141ae7c468b9f53ecb4e58a3302
Source dataset
uspto-grants-2015_08
Patent number
US09115139B2

Reaction notes

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