Potassium Carbonate → Methyl 2-chloro-6-phenylpyridine-3-carboxylate

HRID 2390900Notes

Reaction equation

HRID 2390900 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7](Cl)=[N:6][C:5]=1[Cl:11].[C:13]1(B(O)O)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCCC1>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[N:6][C:5]=1[Cl:11]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 11106516Methyl 2,6-dichloropyridine-3-carboxylate

Product 1

HCID 22484962Methyl 2-chloro-6-phenylpyridine-3-carboxylateYield 47%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To the mixture of 2,6-dichloro-nicotinic acid methyl ester (4.0 g, 19 mmol) synthesized in Example 23 and tetrahydrofuran (39 ml), phenyl boronic acid (2.5 g, 19 mmol), potassium carbonate (8.0 g, 58 mmol), and tetrakis(triphenylphosphine)palladium(0) (1.2 g, 0.97 mmol) were added, and the obtained reaction mixture was stirred for 16 hours while being heated to reflux. The reaction mixture was cooled to room temperature, and then insoluble matter was removed by filtration. The solvents were evaporated under reduced pressure from the filtrate, and then water and ethyl acetate were added to the obtained residue, followed by extraction. The organic layer and the aqueous layer were separated, and the aqueous layer was further extracted using ethyl acetate. The organic layers were mixed, washed with saturated saline, and dried using anhydrous sodium sulfate. The solvents were evaporated under reduced pressure, and the obtained residue was purified with silica gel column chromatography (heptane:ethyl acetate=10:1 to 3:1). The obtained crude compound was recrystallized using the mixed solvent of heptane-diethyl ether, thereby obtaining the entitled compound (2.2 g, 47%).

Workup

  1. additionwere added
  2. customthe obtained reaction mixture
  3. temperaturewhile being heated to reflux
  4. custominsoluble matter was removed by filtration
  5. customThe solvents were evaporated under reduced pressure from the filtrate
  6. additionwater and ethyl acetate were added to the obtained residue
  7. extractionfollowed by extraction
  8. customThe organic layer and the aqueous layer were separated
  9. extractionthe aqueous layer was further extracted
  10. additionThe organic layers were mixed
  11. washwashed with saturated saline
  12. customdried
  13. customThe solvents were evaporated under reduced pressure
  14. customthe obtained residue was purified with silica gel column chromatography (heptane:ethyl acetate=10:1 to 3:1)
  15. customThe obtained crude compound
  16. customwas recrystallized

Sources & evidence

ORD record
ord-ba5f6da305694fc098cc34e138e2166d
Source dataset
uspto-grants-2012_09
Patent number
US08273885B2

Reaction notes

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