6-(Hydroxymethyl)-2-methoxy-4-methylnicotinonitrile → (5-(Aminomethyl)-6-methoxy-4-methylpyridin-2-yl)methanol

HRID 42497Notes

Reaction equation

HRID 42497 reaction equation
[OH:1][CH2:2][C:3]1[CH:10]=[C:9]([CH3:11])[C:6]([C:7]#[N:8])=[C:5]([O:12][CH3:13])[N:4]=1>CC(O)=O.C(O)C.[Ni]>[NH2:8][CH2:7][C:6]1[C:9]([CH3:11])=[CH:10][C:3]([CH2:2][OH:1])=[N:4][C:5]=1[O:12][CH3:13]

Participants

5

Reactant 1

HCID 674676336-(Hydroxymethyl)-2-methoxy-4-methylnicotinonitrile

Product 1

HCID 67468012(5-(Aminomethyl)-6-methoxy-4-methylpyridin-2-yl)methanolYield 58.7%

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 176Acetic AcidSolventHCID 702EthanolSolvent

Procedure

A clear solution of 6-(hydroxymethyl)-2-methoxy-4-methylnicotinonitrile (0.50 g, 2.81 mmol) in HOAc (5 mL) and Ethanol (20 mL) was treated on an H-Cube apparatus (50 psi, 40° C., 1 mL/min., Raney Nickel cartridge) for 18 hr overnight. LCMS showed that the reaction was complete (crude contained 57% product and 43% dimeric side product). The reaction was evaporated to dryness under vacuum. Purified by silica gel chromatography (Analogix, SF25-40 g, 0 to 12% (5% NH4OH in MeOH) in CH2Cl2) (step gradient to 8% to elute off the dimeric side product then to 12% to elute off the product). The pure fractions were combined and evaporated to dryness under vacuum to give the product (5-(aminomethyl)-6-methoxy-4-methylpyridin-2-yl)methanol (0.30 g, 1.646 mmol, 58.7% yield) as a white solid. MS (ES)+m/e 183.1 [M+H]+, 166.1 [M+H]+ −NH3.

Workup

  1. customThe reaction was evaporated to dryness under vacuum
  2. customPurified by silica gel chromatography (Analogix
  3. washSF25-40 g, 0 to 12% (5% NH4OH in MeOH) in CH2Cl2) (step gradient to 8% to elute off the dimeric side product
  4. washto 12% to elute off the product)
  5. customevaporated to dryness under vacuum

Sources & evidence

ORD record
ord-f945f17e09954b6f912ffdfede7fc404
Source dataset
uspto-grants-2013_09
Patent number
US08536179B2

Reaction notes

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