Sodium Carbonate → Methyl 5-(pyrimidin-2-yl)pyridine-3-carboxylate

HRID 454525Notes

Reaction equation

HRID 454525 reaction equation
Br[C:2]1[N:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[Na+].[Na+].CC1(C)C(C)(C)OB([C:22]2[CH:23]=[C:24]([C:28]([O:30][CH3:31])=[O:29])[CH:25]=[N:26][CH:27]=2)O1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O.C(OCC)(=O)C.COCCOC>[N:3]1[CH:4]=[CH:5][CH:6]=[N:7][C:2]=1[C:22]1[CH:23]=[C:24]([C:28]([O:30][CH3:31])=[O:29])[CH:25]=[N:26][CH:27]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 783452-BromopyrimidineHCID 177502573-(Methoxycarbonyl)pyridine-5-boronic acid, pinacol ester

Product 1

HCID 66989995Methyl 5-(pyrimidin-2-yl)pyridine-3-carboxylateYield 36.7%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-Bromopyrimidine (73 mg), sodium carbonate (81 mg), water (0.3 mL), and bis(triphenylphosphine)palladium(II) dichloride (5.3 mg) were added to an ethylene glycol dimethyl ether (1 mL) solution of methyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-carboxylate (0.10 g), followed by heating to reflux under a nitrogen atmosphere for 1 hour and 30 minutes. After cooling the reaction mixture to room temperature, ethyl acetate and water were added thereto, and the insoluble substance was removed by filtration. The organic layer was separated, washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [Fuji Silysia Chemical Ltd., PSQ100B (spherical), eluent: 90-50% hexane/ethyl acetate] to obtain 30 mg of methyl 5-(pyrimidin-2-yl)pyridine-3-carboxylate as a yellow solid.

Workup

  1. temperatureby heating
  2. temperatureto reflux under a nitrogen atmosphere for 1 hour and 30 minutes
  3. customthe insoluble substance was removed by filtration
  4. customThe organic layer was separated
  5. washwashed with a saturated aqueous solution of sodium chloride
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography [Fuji Silysia Chemical Ltd., PSQ100B (spherical), eluent: 90-50% hexane/ethyl acetate]

Sources & evidence

ORD record
ord-a6864ffaf6bc4961bf7ca86798ca0f94
Source dataset
uspto-grants-2013_07
Patent number
US08492582B2

Reaction notes

Loading…