Methanol → Methyl 2-chloro-4-methylpyridine-3-carboxylate

HRID 1959594Notes

Reaction equation

HRID 1959594 reaction equation
[Zn](C)C.[CH3:4][O:5][C:6](=[O:15])[C:7]1[C:12](Br)=[CH:11][CH:10]=[N:9][C:8]=1[Cl:14].[CH3:16]O>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:4][O:5][C:6](=[O:15])[C:7]1[C:12]([CH3:16])=[CH:11][CH:10]=[N:9][C:8]=1[Cl:14]

Participants

6

Reactant 3

HCID 887MethanolHCID 44190945Methyl 4-bromo-2-chloronicotinateHCID 178477796HCID 178477796, compound

Product 1

HCID 17862852Methyl 2-chloro-4-methylpyridine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

ZnMe2 (2.0 M in toluene, 15.5 mL, 25 mmol) was added to a stirred mixture of 4-bromo-2-chloro-nicotinic acid methyl ester (9.6 g, 38 mmol) and Pd(dppf)Cl2 (0.50 g, 0.61 mmol) in anhydrous dioxane (180 mL). After stirring for 8 h at 70° C., the reaction mixture was cooled to room temperature, MeOH (15 mL) was added and the solvent was removed in vacuo. The residue was partitioned between EA (300 mL) and water (50 mL). Concentrated aqueous HCl was then added until the emulsion became homogeneous. The organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (elution with hexane/EA 2:1) to give the title compound. MS (m/z): 186.0 [M+H+].

Workup

  1. temperaturethe reaction mixture was cooled to room temperature
  2. customthe solvent was removed in vacuo
  3. customThe residue was partitioned between EA (300 mL) and water (50 mL)
  4. additionConcentrated aqueous HCl was then added until the emulsion
  5. dry with materialThe organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography on silica gel (elution with hexane/EA 2:1)

Sources & evidence

ORD record
ord-9236a5a400ce455e88f05601d277935f
Source dataset
uspto-grants-2013_04
Patent number
US08410134B2

Reaction notes

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