Benzaldehyde → HCID 15515315, compound

HRID 1976344Notes

Reaction equation

HRID 1976344 reaction equation
Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.[CH:9](=[O:16])[C:10]1C=C[CH:13]=[CH:12][CH:11]=1.C(O)(=O)C1C=CC=CC=1.C(O)CCC#C>C(N(CC)CC)C.Cl[Pd]Cl.[Cu]I.O>[NH2:6][C:5]1[CH:7]=[CH:8][C:2]([C:13]#[C:12][CH2:11][CH2:10][CH2:9][OH:16])=[CH:3][CH:4]=1

Participants

9

Reactant 4

HCID 240BenzaldehydeHCID 243Benzoic AcidHCID 78074-BromoanilineHCID 793464-Pentyn-1-ol

Product 1

HCID 15515315HCID 15515315, compoundYield 130.1%

Reagents, catalysts & solvents 4

HCID 24290Palladium ChlorideCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 8471TriethylamineSolvent2×

Conditions

Temperature
50 °C

Procedure

A mixture of 4-bromoaniline (1.72 g, 10 mmol), benzaldehyde (0.27 g, 2.5 mmol), benzoic acid (0.05 g, 0.4 mmol), PdCl2 (2 mg) and triethylamine (3.5 g) was deaerated by bubbling nitrogen and then heated to reflux for 45 min. Thin-layer chromatography showed the formation of N-benzylidene 4-aminophenylbromide). The reaction mixture was cooled to 50° C. and treated with triphenylphosphine (73 mg in 1 g of triethylamine) followed by a slurry of CuI (20 mg) and 4-pentyn-1-ol (1.1 g, 13 mmol). This reaction mixture was heated at reflux for 10 hr. The mixture was cooled and diluted with triethylamine (5 mL) and treated with water (6 mL). The aqueous layer was separated and the triethylamine layer was concentrated under vacuum. Toluene was added and the mixture again concentrated. Then aqueous HCl (10 mL, 7%) was added. The resulting aqueous solution was cooled, basified with 50% NaOH, and extracted with ethyl acetate. The ethyl acetate extract was evaporated under vacuum and the residue was flash chromatographed (20% ethyl acetate-dichloromethane, silica) to yield 0.57 g of 5-(4-aminophenyl)-4-pentyn-1-ol as an oil.

Workup

  1. customby bubbling nitrogen
  2. temperatureheated
  3. temperatureto reflux for 45 min
  4. additiontreated with triphenylphosphine (73 mg in 1 g of triethylamine)
  5. temperatureThis reaction mixture was heated
  6. temperatureat reflux for 10 hr
  7. temperatureThe mixture was cooled
  8. customThe aqueous layer was separated
  9. concentrationthe triethylamine layer was concentrated under vacuum
  10. additionToluene was added
  11. concentrationthe mixture again concentrated
  12. additionThen aqueous HCl (10 mL, 7%) was added
  13. temperatureThe resulting aqueous solution was cooled
  14. extractionextracted with ethyl acetate
  15. extractionThe ethyl acetate extract
  16. customwas evaporated under vacuum
  17. customchromatographed (20% ethyl acetate-dichloromethane, silica)

Sources & evidence

ORD record
ord-b644c7b12d214da59bf900a3b7864d72
Source dataset
uspto-grants-2001_05
Patent number
US06225499B1

Reaction notes

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