Triethylamine → 6-Dodec-1-ynylnicotinaldehyde

HRID 735948Notes

Reaction equation

HRID 735948 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][N: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].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C>C1COCC1.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[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][N: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 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 698211-DodecyneHCID 117692346-Bromo-3-pyridinecarboxaldehyde

Product 1

HCID 865985376-Dodec-1-ynylnicotinaldehydeYield 29.9%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 6-bromonicotinaldehyde (500 mg, 2.69 mmol), 1-dodecyne (680 mg, 4.09 mmol), triphenylphosphine (23 mg, 0.09 mmol), triethylamine (470 ml, 3.38 mmol) and bis(triphenylphosphine)palladium(II) chloride (94 mg, 0.13 mmol) in THF (10 mL) was stirred under argon at rt for 30 min. Copper(I) iodide (21 mg, 0.11 mmol) was added and the mixture was stirred for 21 hours at rt. The solvent was removed under reduced pressure. The residue was diluted with a saturated aqueous solution of NH4Cl (20 mL) and extracted with Et2O (50 ml+2×20 mL). The combined organic layers were dried over MgSO4 and the solvent was removed under reduce pressure. The residue was purified by flash chromatography (c-Hex/EtOAc 4/1) to give the title compound as yellow oil (218 mg, 29%). 1H NMR (CDCl3, 300 MHz) δ 10.1 (s, 1H), 9.00 (s, 1H), 8.11 (d, 1H, J=8.1 Hz), 7.52 (d, 1H, J=8.1 Hz), 2.49 (t, 2H, J=7.1 Hz), 1.67 (m, 2H), 1.47 (m, 2H), 1.28 (m, 12H), 0.89 (t, 3H, J=6.8 Hz). M−(LC/MS(ESI)): 270.3; M+(LC/MS(ESI)): 272.4. HPLC (Condition A), Rt: 5.23 min (HPLC purity: 98.3%).

Workup

  1. stirringthe mixture was stirred for 21 hours at rt
  2. customThe solvent was removed under reduced pressure
  3. additionThe residue was diluted with a saturated aqueous solution of NH4Cl (20 mL)
  4. extractionextracted with Et2O (50 ml+2×20 mL)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. customthe solvent was removed
  7. customThe residue was purified by flash chromatography (c-Hex/EtOAc 4/1)

Sources & evidence

ORD record
ord-1d366b9745e4409ca42d7dd6bd23a3e7
Source dataset
uspto-grants-2009_09
Patent number
US07592477B2

Reaction notes

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