Piperidine → 6-(4-Fluoro-phenyl)-5-piperidin-1-yl-pyrazine-2-carboxylic acid methyl ester

HRID 639343Notes

Reaction equation

HRID 639343 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:7][O:8][C:9]([C:11]1[CH:16]=[N:15][C:14](Br)=[C:13]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[N:12]=1)=[O:10]>C(#N)C>[CH3:7][O:8][C:9]([C:11]1[CH:16]=[N:15][C:14]([N:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)=[C:13]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[N:12]=1)=[O:10]

Participants

4

Reactant 2

HCID 8082PiperidineHCID 866169575-Bromo-6-(4-fluoro-phenyl)-pyrazine-2-carboxylic acid methyl ester

Product 1

HCID 675048406-(4-Fluoro-phenyl)-5-piperidin-1-yl-pyrazine-2-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Piperidine (0.48 ml, 4.82 mmol, 2.0 eq) was added portion-wise to a acetonitrile (2 ml) solution of 5-bromo-6-(4-fluoro-phenyl)-pyrazine-2-carboxylic acid methyl ester (0.75 g, 2.41 mmol, 1.0 eq) at room temperature. The mixture was irradiated at 100° C. in a microwave with stirring for 30 minutes. HPLC-MS indicated complete consumption of starting material. The crude mixture was cooled to room temperature concentrated. The residue was re-dissolved in ethyl acetate (10 ml), washed with water (5 ml) and the organic phase dried over MgSO4. Following filtration and evaporation in vacuo, the residue was purified by chromatography on silica gel using a gradient of heptane to 10% ethyl acetate in heptane to afford 6-(4-fluoro-phenyl)-5-piperidin-1-yl-pyrazine-2-carboxylic acid methyl ester. Yield=0.48 g (63%). 1H NMR (250 MHz, CDCl3): δ 1.42-1.53 (6H, m), 3.20-3.24 (4H, m), 3.88 (3H, s), 7.06 (2H, t, J=8.78 Hz), 7.74-7.80 (2H, m), 8.68 (1H, s).

Workup

  1. customThe mixture was irradiated at 100° C. in a microwave
  2. customconsumption of starting material
  3. concentrationconcentrated
  4. dissolutionThe residue was re-dissolved in ethyl acetate (10 ml)
  5. washwashed with water (5 ml)
  6. dry with materialthe organic phase dried over MgSO4
  7. filtrationfiltration and evaporation in vacuo
  8. customthe residue was purified by chromatography on silica gel using a gradient of heptane to 10% ethyl acetate in heptane

Sources & evidence

ORD record
ord-efc447f3ec1c4accb74cda9104bfd5fd
Source dataset
uspto-grants-2010_04
Patent number
US07691863B2

Reaction notes

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