Sulfuric Acid → Ethyl 3-hydroxyisonicotinate

HRID 2109051Notes

Reaction equation

HRID 2109051 reaction equation
N[C:2]1[CH:12]=[N:11][CH:10]=[CH:9][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5].S(=O)(=O)(O)[OH:14].N([O-])=O.[Na+].C(=O)([O-])O.[Na+]>O>[OH:14][C:2]1[CH:12]=[N:11][CH:10]=[CH:9][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5]

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 516892Sodium BicarbonateHCID 2736365Ethyl 3-AminoisonicotinateHCID 23668193Sodium Nitrite

Product 1

HCID 12326192Ethyl 3-hydroxyisonicotinate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent3×

Procedure

Ethyl 3-aminoisonicotinate (5.55 g) is suspended in water (70 ml), and thereto added conc. sulfuric acid (4.0 ml). The reaction solution is cooled with ice, and a solution of sodium nitrite (2.79 g) in water (30 ml) is added dropwise thereto. The reaction solution is stirred under the same cooling conditions for 20 minutes and then at 90° C. for 80 minutes. The reaction solution is diluted with water (100 ml) and the solution is adjusted to pH 8 to 9 by addition of saturated aqueous sodium hydrogen carbonate solution, followed by extraction with chloroform. The organic layer is dried over sodium sulfate and evaporated to remove the solvent under reduced pressure. The resulting residue is purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=5/1) to give ethyl 3-hydroxyisonicotinate (2.64 g).

Workup

  1. temperatureThe reaction solution is cooled with ice
  2. temperaturesame cooling conditions for 20 minutes
  3. extractionfollowed by extraction with chloroform
  4. dry with materialThe organic layer is dried over sodium sulfate
  5. customevaporated
  6. customto remove the solvent under reduced pressure
  7. customThe resulting residue is purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=5/1)

Sources & evidence

ORD record
ord-b3701f335155479b93e5a93e0afe6245
Source dataset
uspto-grants-2009_04
Patent number
US07514449B2

Reaction notes

Loading…