Potassium Carbonate → Methyl 6-chloro-5-methylpyridine-3-carboxylate

HRID 420722Notes

Reaction equation

HRID 420722 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[CH:5]=[N:6][C:7]=1[Cl:8].[C:13]([O-])([O-])=O.[K+].[K+].[CH3:19]B1OB(C)OB(C)O1>O1CCOCC1.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>[Br:1][C:2]1[CH:3]=[C:4]([CH:9]=[O:11])[CH:5]=[N:6][C:7]=1[CH3:13].[Cl:8][C:7]1[N:6]=[CH:5][C:4]([C:9]([O:11][CH3:12])=[O:10])=[CH:3][C:2]=1[CH3:19]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 2764313Methyl 5-bromo-6-chloronicotinate

Product 2

HCID 12404031Methyl 6-chloro-5-methylpyridine-3-carboxylateHCID 534851635-Bromo-6-methylpyridine-3-carbaldehyde

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture of methyl 5-bromo-6-chloro-3-pyridinecarboxylate (400 mg, 1.597 mmol), tetrakis(triphenylphosphine)palladium (0) (185 mg, 0.160 mmol), and K2CO3 (331 mg, 2.395 mmol) in dioxane (5 ml), trimethylboroxin (0.446 ml, 3.19 mmol) was added under argon. The reaction mixture was heated at 110° C. for 5 h. The reaction mixture was allowed to cool down, filtered through a pad of silica, and concentrated to give 176 mg of the crude material. Purification by flash chromatography using Flashmaster II, a 5 g spherical silica gel cartridge, and mixtures of hexane and DCM as eluent afforded 76 mg of desired compound and 84 mg of methyl 6-chloro-5-methyl-3-pyridinecarboxylate as by-product.

Workup

  1. additionwas added under argon
  2. temperatureto cool down
  3. filtrationfiltered through a pad of silica
  4. concentrationconcentrated
  5. customto give 176 mg of the crude material
  6. customPurification by flash chromatography

Sources & evidence

ORD record
ord-267e242f5edd477e88b7abcb88b10bef
Source dataset
uspto-grants-2012_01
Patent number
US08097628B2

Reaction notes

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