Triethylamine → 6-(1-Dodecynyl)-2-pyridinecarboxaldehyde

HRID 375954Notes

Reaction equation

HRID 375954 reaction equation
Br[C:2]1[N:7]=[C:6]([CH:8]=[O:9])[CH:5]=[CH:4][CH:3]=1.[CH:10]#[C:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21].C(N(CC)CC)C>O1CCCC1.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.[Cu]I>[C:10]([C:2]1[N:7]=[C:6]([CH:8]=[O:9])[CH:5]=[CH:4][CH:3]=1)#[C:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]

Participants

8

Reactant 3

HCID 8471Triethylamine2×HCID 698211-Dodecyne3×HCID 27570096-Bromopyridine-2-carbaldehyde

Product 1

HCID 183731096-(1-Dodecynyl)-2-pyridinecarboxaldehydeYield 29%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
40 °C

Procedure

To a solution of 6-bromo-2-pyridinecarboxaldehyde (3.0 g) in tetrahydrofuran (10 ml), was added sequentially bis(triphenylphosphine)palladium(II) chloride (0.178 g), copper(I)iodide (0.024 g), 1-dodecyne (3.25 ml), and triethylamine (2.12 ml). The solution was stirred at 40° C. overnight. The reaction mixture was cooled to room temperature, charged again with bis(triphenylphosphine)palladium (II) chloride (0.024 g), copper (I) iodide (0.024 g), and triethylamine (2.12 ml), and 1-dodecyne (3.25 ml), and tetrahydrofuran (5.0 ml), and heated at 40° C. for 5 hrs. The reaction mixture was again cooled and recharged as above, and heated lit 40° C. for 24 hrs. The cooled mixture was concentrated, taken up in ethyl acetate (100 ml), washed with water and saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The residue was taken up in ethyl acetate (100 ml) and filtered. The filtrate was combined with material from a similar reaction run 1.43 g of the carboxaldehyde and proportionate amounts of the catalysts, 1-dodecyne, and solvent. The filtrate was concentrated. The residue was purified by flash chromatography using 1.5% ethyl acetate/hexane followed by 1% ethyl acetate/hexane as eluents. The appropriate fractions were collected and concentrated to yield 2.24 g (29%) of product, as an oil.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. temperatureheated at 40° C. for 5 hrs
  3. temperatureThe reaction mixture was again cooled
  4. temperatureheated
  5. waitlit 40° C. for 24 hrs
  6. concentrationThe cooled mixture was concentrated
  7. washwashed with water and saturated sodium chloride solution
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated
  11. filtrationfiltered
  12. customThe filtrate was combined with material from a similar reaction
  13. concentrationThe filtrate was concentrated
  14. customThe residue was purified by flash chromatography
  15. customThe appropriate fractions were collected
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-d479c0b03c04427899a1a5b4bc02dbfb
Source dataset
uspto-grants-1996_01
Patent number
US05488063

Reaction notes

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