Benzyl Alcohol → Isonicotinic Acid

HRID 336511Notes

Reaction equation

HRID 336511 reaction equation
[Na].[K].C(O)C=C.C(O)C1C=CC=CC=1.Cl[C:16]1[CH:17]=[C:18]([CH:22]=[C:23](Cl)[N:24]=1)[C:19]([OH:21])=[O:20]>O.CN(C)C=O.C1(C)C=CC=CC=1.O1CCCC1>[C:19]([OH:21])(=[O:20])[C:18]1[CH:22]=[CH:23][N:24]=[CH:16][CH:17]=1

Participants

10

Reactant 5

HCID 244Benzyl AlcoholHCID 7858Allyl AlcoholHCID 948302,6-Dichloroisonicotinic acid2×HCID 5360545Sodium3×HCID 5462222Potassium

Product 1

HCID 5922Isonicotinic Acid

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

A sodium or potassium salt of allyl alcohol, benzyl alcohol, or substituted benzyl alcohol is dissolved in a solvent that does not affect the reaction, such as tetrahydrofuran, toluene, and dimethylformamide, and preferably dimethylformamide. A sodium salt of 2,6-dichloroisonicotinic acid is added to the resulting solution at room temperature. The resulting mixture is stirred at 60 to 100° C. for 2 to 24 hours. The mixture is allowed to react, preferably, at 80° C. for 4 hours. Here, 2 to 10 equivalent, and preferably 4 equivalent amount of alcoholate is used relative to a sodium salt of 2,6-dichloroisonicotinic acid. After the reaction has completed, water is added to the reaction product, and a water layer is separated using ethyl acetate or a like solvent. The pH of the water layer is adjusted to 5 to 6 using 1N-hydrochloric acid or acetic acid. The result is subjected to extraction using ethyl acetate, a mixed solvent of ethyl acetate and n-hexane, toluene, or the like. The extract is dried over sodium sulfate, magnesium sulfate, etc., and then concentrated to obtain an isonicotinic acid derivative of allyloxy, benzyloxy, or substituted benzyloxy (2)(in the present specification, the isonicotinic acid derivative of allyloxy, benzyloxy, or substituted benzyloxy (2) may be referred to as isonicotinic acid derivative (2)).

Workup

  1. customthe reaction
  2. customto react
  3. waitpreferably, at 80° C. for 4 hours
  4. customa water layer is separated
  5. extractionThe result is subjected to extraction
  6. dry with materialThe extract is dried over sodium sulfate, magnesium sulfate, etc.
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-5192412b7d5643c69209ec2639e0006c
Source dataset
uspto-grants-2014_11
Patent number
US08889699B2

Reaction notes

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