Sodium Azide → 6-(Aminomethyl)picolinonitrile

HRID 1711144Notes

Reaction equation

HRID 1711144 reaction equation
[N-:1]=[N+]=[N-].[Na+].Br[CH2:6][C:7]1[N:12]=[C:11]([C:13]#[N:14])[CH:10]=[CH:9][CH:8]=1>CN(C=O)C.CO.[Pd]>[NH2:1][CH2:6][C:7]1[N:12]=[C:11]([C:13]#[N:14])[CH:10]=[CH:9][CH:8]=1

Participants

6

Reactant 2

HCID 33557Sodium AzideHCID 272816606-(Bromomethyl)pyridine-2-carbonitrile

Product 1

HCID 104643836-(Aminomethyl)picolinonitrileYield 46.4%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

Sodium azide (0.280 g, 4.32 mmol) was added to a solution of 6-bromomethyl-pyridine-2-carbonitrile (0.610 g, 2.88 mmol) in DMF (12 ml) and the resulting pale yellow solution was stirred at rt for 16 h. Standard basic workup gave the crude product as a tan solid in quantitative yield (0.501 g). The crude solid was dissolved in MeOH (15 ml), treated with 10% Pd/C (0.050 g) and placed under 40 psi H2 on a Parr shaker for 30 minutes (Note: it is imperative that this reduction is stopped at 30 minutes or reduction of the nitrile also occurs). The mixture was filtered through Celite®, the cake was washed with MeOH and the combined filtrate was concentrated under reduced pressure to give a yellow oil. Purification by column chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 83:15:2, v/v/v) afforded 6-aminomethyl-pyridine-2-carbonitrile (0.178 g, 46%) as a white crystalline solid. 1H NMR (CDCl3) δ 1.96 (br s, 2H), 4.02 (s, 2H), 7.53 (d, 1H, J=9.0 Hz), 7.59 (d, 1H, J=9.0 Hz), 7.80 (t, 1H, J=9.0 Hz).

Workup

  1. customStandard basic workup gave the crude product as a tan solid in quantitative yield (0.501 g)
  2. waitplaced under 40 psi H2 on a Parr shaker for 30 minutes
  3. waitis stopped at 30 minutes
  4. filtrationThe mixture was filtered through Celite®
  5. washthe cake was washed with MeOH
  6. concentrationthe combined filtrate was concentrated under reduced pressure
  7. customto give a yellow oil
  8. customPurification by column chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 83:15:2, v/v/v)

Sources & evidence

ORD record
ord-a557dcb2100a49ff9cc991078e5f62f6
Source dataset
uspto-grants-2010_09
Patent number
US07790747B2

Reaction notes

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