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

HRID 743776Notes

Reaction equation

HRID 743776 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.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[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

7

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalyst2×HCID 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 (1) 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 at 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 at 40° C. for 24 hrs
  5. concentrationThe cooled mixture was concentrated
  6. washwashed with water and saturated sodium chloride solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationthe filtrate was concentrated
  10. filtrationfiltered
  11. customThe filtrate was combined with material from a similar reaction
  12. concentrationThe filtrate was concentrated
  13. customThe residue was purified by flash chromatography
  14. customThe appropriate fractions were collected
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-4c5abde33e88422fa8cc0747315ab627
Source dataset
uspto-grants-1996_09
Patent number
US05557006

Reaction notes

Loading…