Propargyl alcohol → 2-hydroxymethyl-1H-indole-5-carbaldehyde

HRID 591675Notes

Reaction equation

HRID 591675 reaction equation
[CH:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=O)[CH3:11])=[C:5](I)[CH:4]=1)=[O:2].CN(C)C(N(C)C)=N.[CH2:22]([OH:25])C#C>CN(C=O)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>[OH:25][CH2:22][C:10]1[NH:9][C:6]2[C:7]([CH:11]=1)=[CH:8][C:3]([CH:1]=[O:2])=[CH:4][CH:5]=2

Participants

7

Reactant 3

HCID 7859Propargyl alcoholHCID 664601,1,3,3-TetramethylguanidineHCID 229919464-Acetamido-3-iodobenzaldehyde

Product 1

HCID 866620272-hydroxymethyl-1H-indole-5-carbaldehyde

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

To a degassed solution of N-(4-formyl-2-iodo-phenyl)-acetamide (0.760 g, 2.63 mmol) in anhydrous DMF (20 mL) were added bis(triphenylphosphine)palladium(II) dichloride (90 mg, 0.13 mmol), copper (I) iodide (0.03 g, 0.13 mmol), 1,1,3,3-tetramethyl guanidine (1.51 g, 13.1 mmol), and propargyl alcohol (0.210 g, 3.68 mmol). The reaction mixture was stirred at room temperature for 2 hours and then at 80° C. for 24 hours under nitrogen. Solvent was evaporated under reduced pressure. Water (100 mL) was added and the mixture was extracted with ethyl acetate (200 mL). The organic phase was backwashed with water (2×100 mL), brine (100 mL), and dried over anhydrous Na2SO4. Solvent was evaporated and crude compound was purified by the Simpliflash system (60% ethyl acetate in hexanes as eluent) to give 2-hydroxymethyl-1H-indole-5-carbaldehyde as a pale yellow solid. Yield: 0.10 g (22%).

Workup

  1. waitat 80° C. for 24 hours under nitrogen
  2. customSolvent was evaporated under reduced pressure
  3. additionWater (100 mL) was added
  4. extractionthe mixture was extracted with ethyl acetate (200 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. customSolvent was evaporated
  7. customcrude compound was purified by the Simpliflash system (60% ethyl acetate in hexanes as eluent)

Sources & evidence

ORD record
ord-693604ae779f4ca482f4ba8636b6d6b6
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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