Potassium Carbonate → Methyl 5-ethynylnicotinate

HRID 2407428Notes

Reaction equation

HRID 2407428 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[C:12]([Si](C)(C)C)#[CH:13].C(=O)([O-])[O-].[K+].[K+]>[Cu]I.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>[CH3:10][O:9][C:7](=[O:8])[C:6]1[CH:11]=[C:2]([C:12]#[CH:13])[CH:3]=[N:4][CH:5]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 66111TrimethylsilylacetyleneHCID 699336Methyl 5-bromopyridine-3-carboxylate

Product 1

HCID 53898384Methyl 5-ethynylnicotinate

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalyst

Conditions

Temperature
50 °C

Procedure

To methyl 5-bromonicotinate (3.0 g, 13.89 mmol) in TEA (50 mL) under N2 was added ethynyltrimethylsilane (5.83 mL, 41.7 mmol), copper(I) iodide (0.132 g, 0.694 mmol) and bis(triphenylphosphine)palladium(II) chloride (0.487 g, 0.694 mmol). The reaction was stirred at 50° C. for 1 h. The reaction was cooled to room temperature and filtered to remove the solids. The precipitate was washed thoroughly with ethyl acetate. The filtrate was then washed with water twice and extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo to afford a black color solid. Assuming 100% conversion this was taken on to next step for TMS removal. The crude was dissolved in MeOH (50 mL) and potassium carbonate (0.480 g, 3.47 mmol) was added to it. The reaction mixture was stirred for 30 min. The solids were filtered off, the filtrate was concentrated in vacuo. The crude was purified by silica gel flash chromatography using DCM-MeOH: 90-10 to give pure product 5-Ethynyl-nicotinic acid methyl ester as a light yellow solid. ESI-MS: m/z 162.1 (M+H)+

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. filtrationfiltered
  3. customto remove the solids
  4. washThe precipitate was washed thoroughly with ethyl acetate
  5. washThe filtrate was then washed with water twice
  6. extractionextracted with ethyl acetate
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customto afford a black color solid
  10. customthis was taken on to next step for TMS removal
  11. dissolutionThe crude was dissolved in MeOH (50 mL)
  12. stirringThe reaction mixture was stirred for 30 min
  13. filtrationThe solids were filtered off
  14. concentrationthe filtrate was concentrated in vacuo
  15. customThe crude was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-d7674008b95f4c6ea00f75db1cfd5f51
Source dataset
uspto-grants-2014_08
Patent number
US08809545B2

Reaction notes

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