Hydrochloric Acid → 6-[(4-Butylphenyl)ethynyl]nicotinaldehyde

HRID 733626Notes

Reaction equation

HRID 733626 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][N:3]=1.CCN(CC)CC.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[CH2:36]([C:40]1[CH:45]=[CH:44][C:43]([C:46]#[CH:47])=[CH:42][CH:41]=1)[CH2:37][CH2:38][CH3:39].Cl>[Cu]I.CC([O-])=O.CC([O-])=O.[Pd+2].C1COCC1>[CH2:36]([C:40]1[CH:41]=[CH:42][C:43]([C:46]#[C:47][C:2]2[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][N:3]=2)=[CH:44][CH:45]=1)[CH2:37][CH2:38][CH3:39]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 27751321-Butyl-4-ethynylbenzeneHCID 117692346-Bromo-3-pyridinecarboxaldehyde

Product 1

HCID 114028186-[(4-Butylphenyl)ethynyl]nicotinaldehydeYield 34.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
70 °C

Procedure

To a solution of 6-bromo-nicotinaldehyde (9.3 g, 50 mmol), Et3N (15.2 g, 150 mmol), CuI (190 mg, 1.0 mmol) and PPh3 (1.05 g, 4.0 mmol) in anhydrous degassed THF (250 mL) was added Pd(OAc)2 (225 mg, 1 mmol). The mixture was heated at 70° C. for 30 min. Then, a solution of 1-butyl-4-eth-1-ynylbenzene (11.9 g, 75 mmol) in anhydrous degassed THF (1M) was added dropwise. The reaction mixture was stirred at 70° C. for 15 h. Then, an aqueous solution of HCl 1N was added and the resulting mixture was extracted with Et2O (3×). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure to give an orange oil. Purification by chromatography on silica gel (c-Hex/EtOAc 85/15) gave 4.5 g of the title compound as an orange oil (34%). M+ (ESI): 264.3. HPLC, Rt: 4.87 min (purity: 96.7%).

Workup

  1. additionwas added dropwise
  2. extractionthe resulting mixture was extracted with Et2O (3×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give an orange oil
  8. customPurification by chromatography on silica gel (c-Hex/EtOAc 85/15)

Sources & evidence

ORD record
ord-b67eb1c8125e45feb3633b4884b205b8
Source dataset
uspto-grants-2009_09
Patent number
US07589232B2

Reaction notes

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