Nicotinic Acid → Chloromethyl nicotinate

HRID 1863863Notes

Reaction equation

HRID 1863863 reaction equation
[C:1]([OH:9])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.C(=O)(O)[O-].[Na+].S([O-])([O-])(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC.[Cl:54][CH2:55]S(Cl)(=O)=O>ClCCl.O>[N:4]1[CH:5]=[CH:6][CH:7]=[C:2]([C:1]([O:9][CH2:55][Cl:54])=[O:8])[CH:3]=1

Participants

7

Reactant 4

HCID 938Nicotinic AcidHCID 77054(Chloromethyl)sulfonyl chlorideHCID 516892Sodium BicarbonateHCID 11433187Bis(tetrabutylammonium) sulphate

Product 1

HCID 14608830Chloromethyl nicotinateYield 25.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A mixture of nicotinic acid (200 mg, 1.6 mmol), sodium bicarbonate (540 mg, 6.4 mmol), and tetrabutylammonium sulfate (54 mg, 0.16 mmol) was dissolved in a mixture of 4 ml of dichloromethane and 4 ml of water, and cooled to 0° C. To this stirred mixture was added chloromethylchlorosulfone (165 μl, 1.6 mmol) in 1 ml of dichloromethane, and the mixture was allowed to warm to room temperature, stirring overnight. The organic layer was separated, washed with brine, dried over sodium sulfate, and concentrated under reduced pressure to a yellow oil, which was dissolved in dichloromethane and filtered through a silica plug. Removal of the solvent under reduced pressure provided chloromethyl pyridine-3-carboxylate (70 mg).

Workup

  1. temperatureto warm to room temperature
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure to a yellow oil, which
  6. dissolutionwas dissolved in dichloromethane
  7. filtrationfiltered through a silica plug
  8. customRemoval of the solvent under reduced pressure

Sources & evidence

ORD record
ord-181dd5b749dd4638b60d7947e187bb4e
Source dataset
uspto-grants-2009_12
Patent number
US07625881B2

Reaction notes

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