Methanol → Methyl 5-chloropyridine-3-carboxylate

HRID 512139

Reaction equation

HRID 512139 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].S(Cl)(Cl)=O.[CH3:15]O>C(=O)(O)[O-].[Na+]>[CH3:15][O:8][C:7](=[O:9])[C:6]1[CH:10]=[C:2]([Cl:1])[CH:3]=[N:4][CH:5]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 24386Thionyl ChlorideHCID 2479865-Chloronicotinic acid

Product 1

HCID 15421663Methyl 5-chloropyridine-3-carboxylateYield 79%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 5-chloro-nicotinic acid (20.0 g, 127 mmol, purchased from Matrix Scientific, Columbia, S.C., USA) in methanol (200 mL) at 0° C. was added thionyl chloride (18.6 mL, 255 mmol). The reaction mixture was refluxed for 4 hours. After cooling to room temperature the mixture was diluted with saturated aqueous sodium bicarbonate, extracted with AcOEt (3×300 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to afford crude 5-chloro-nicotinic acid methyl ester (17.2 g, 79%). 1H NMR (400 MHz, CDCl3) δ ppm 9.10 (d, J=1.4 Hz, 1 H), 8.75 (d, J=2.3 Hz, 1 H), 8.29 (d, J=2.0 Hz, 1H), 3.98 (s, 3 H). MS m/z 171.8

Workup

  1. temperatureThe reaction mixture was refluxed for 4 hours
  2. extractionextracted with AcOEt (3×300 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-4477b706be4d4747844e2f2673844d78
Source dataset
uspto-grants-2015_08
Patent number
US09102591B2

Linked notes

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