Ethyl Acetate → Methyl 5-(dimethylamino)nicotinate

HRID 1784941Notes

Reaction equation

HRID 1784941 reaction equation
N[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[BH3-][C:13]#[N:14].[Na+].[CH3:16]COC(C)=O.C([O-])(O)=O.[Na+]>CC#N.C=O.O.C(O)(=O)C>[CH3:16][N:14]([CH3:13])[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8]

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 1514432Methyl 5-aminopyridine-3-carboxylateHCID 5003444Sodium cyanoborohydride

Product 1

HCID 23271121Methyl 5-(dimethylamino)nicotinateYield 37%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidCatalystHCID 712FormaldehydeSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a stirring solution of 283 mg (1.86 mmol) of methyl 5-aminonicotinate in 19 mL of CH3CN and 19 mL of 37% formaldehyde in H2O was added 353 mg (5.62 mmol) of NaCNBH3, and 50 drops of acetic acid. The solution was stirred at r.t. for 18.5 h and 40 mL of EtOAc and 40 mL of sat. NaHCO3 solution was added. The layers were separated, and the organic layer was washed with 25 mL of sat. NaHCO3 and 25 mL of brine, dried over Na2SO4, filtered, and concentrated. Purification by flash silica gel chromatography (0.5% MeOH/CHCl3) resulted in 124 mg of methyl 5-(dimethylamino)nicotinate as a yellow oil in 37% yield.

Workup

  1. customThe layers were separated
  2. washthe organic layer was washed with 25 mL of sat. NaHCO3 and 25 mL of brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by flash silica gel chromatography (0.5% MeOH/CHCl3)
  7. customresulted in 124 mg of methyl 5-(dimethylamino)nicotinate as a yellow oil in 37% yield

Sources & evidence

ORD record
ord-7510fa7a762643ae9c45bf10b60c631c
Source dataset
uspto-grants-2009_03
Patent number
US07504420B2

Reaction notes

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