Tetrahydrofuran → 2-Methyl-6-[(1-methylpiperidin-4-yl)-methyl]-3-nitropyridine

HRID 1892201

Reaction equation

HRID 1892201 reaction equation
B1C2CCCC1CCC2.C1COCC1.[CH3:15][N:16]1[CH2:21][CH2:20][C:19](=[CH2:22])[CH2:18][CH2:17]1.C[C:24]1[CH:29]=[CH:28][C:27]([N+:30]([O-:32])=[O:31])=[C:26]([CH3:33])[N:25]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH3:33][C:26]1[C:27]([N+:30]([O-:32])=[O:31])=[CH:28][CH:29]=[C:24]([CH2:22][CH:19]2[CH2:20][CH2:21][N:16]([CH3:15])[CH2:17][CH2:18]2)[N:25]=1

Participants

8

Reactant 5

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 789669-Borabicyclo(3.3.1)nonaneHCID 849582,6-Dimethyl-3-nitropyridineHCID 139537Piperidine, 1-methyl,4-methylene-

Product 1

HCID 584766172-Methyl-6-[(1-methylpiperidin-4-yl)-methyl]-3-nitropyridineYield 11.5%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of 9-BBN in THF (0.5 M, 4.93 mL, 2.46 mmol) was added 1-methyl-4-methylenepiperidine (274 mg, 2.46 mmol). The reaction mixture was allowed to stir at 75° C. for 1 h and was then allowed to cool to rt. The resulting solution was transferred into a solution of 2-methyl-5-nitro-6-methylpyridine (486 mg, 2.24 mmol) in DMF (11 mL). To the mixture were added [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (1:1 complex with DCM, 54.9 mg, 0.0672 mmol) and potassium carbonate (402 mg, 2.91 mmol). The reaction mixture was allowed to stir for 3 h at rt. The mixture was quenched by the addition of water (10 mL). The aqueous solution was extracted with DCM. The organic solutions were combined, washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to give 2-methyl-6-[(1-methylpiperidin-4-yl)-methyl]-3-nitropyridine (64 mg, 10%) as a white solid. LCMS (FAL): Rt=3.38 min, m/z=250.2 (M+H).

Workup

  1. temperatureto cool to rt
  2. stirringto stir for 3 h at rt
  3. customThe mixture was quenched by the addition of water (10 mL)
  4. extractionThe aqueous solution was extracted with DCM
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-d2cf6a676e91441b8fe3da07ecb80fa3
Source dataset
uspto-grants-2013_08
Patent number
US08507667B2

Linked notes

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