3-Butyn-1-OL → N-[4-formyl-2-(4-hydroxy-but-1-ynyl)-phenyl]-acetamide

HRID 591680Notes

Reaction equation

HRID 591680 reaction equation
[CH:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:12])[CH3:11])=[C:5](I)[CH:4]=1)=[O:2].[CH2:14]([OH:18])[CH2:15][C:16]#[CH:17]>CN(C=O)C.C(N(CC)CC)C.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>[CH:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:12])[CH3:11])=[C:5]([C:17]#[C:16][CH2:15][CH2:14][OH:18])[CH:4]=1)=[O:2]

Participants

7

Reactant 2

HCID 135663-Butyn-1-OLHCID 229919464-Acetamido-3-iodobenzaldehyde

Product 1

HCID 86662028N-[4-formyl-2-(4-hydroxy-but-1-ynyl)-phenyl]-acetamide

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent2×HCID 8471TriethylamineSolvent2×

Conditions

Temperature
80 °C

Procedure

To a degassed solution of N-(4-formyl-2-iodo-phenyl)-acetamide (0.810 g, 2.82 mmol) in DMF (25 mL) and triethylamine (5 mL) were added PdCl2(PPh3)2 (0.10 g, 0.14 mmol) and copper (I) iodide (0.16 g, 0.85 mmol). A degassed solution of but-3-yn-1-ol (0.27 g, 0.29 mmol) in DMF (8 mL) and triethylamine (2 mL) was added at 80° C. over a period of 1 hour under nitrogen. After the addition, the reaction mixture was stirred at 80° C. for 4 hours, cooled to room temperature, and concentrated under reduced pressure. The residue was diluted with water (100 mL) and extracted with ethyl acetate (200 mL). The organic phase was washed with brine (100 mL) and dried over anhydrous Na2SO4. Removal of solvent gave N-[4-formyl-2-(4-hydroxy-but-1-ynyl)-phenyl]-acetamide as a brown solid. Crude yield: 0.85 g (100%). The crude material was used in next step without further purification.

Workup

  1. additionAfter the addition
  2. temperaturecooled to room temperature
  3. concentrationconcentrated under reduced pressure
  4. additionThe residue was diluted with water (100 mL)
  5. extractionextracted with ethyl acetate (200 mL)
  6. washThe organic phase was washed with brine (100 mL)
  7. dry with materialdried over anhydrous Na2SO4
  8. customRemoval of solvent

Sources & evidence

ORD record
ord-1dfd0c9d8ca642598fc46de7d3ea8380
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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