Propargyl alcohol → HCID 58485659, compound

HRID 1012725Notes

Reaction equation

HRID 1012725 reaction equation
[CH2:1]([OH:4])[C:2]#[CH:3].[N:5]12[CH2:12][CH2:11][CH:8]([CH2:9][CH2:10]1)[C@@H:7]([NH:13][C:14]([C:16]1[O:17][C:18]3[CH:24]=[C:23](Br)[CH:22]=[CH:21][C:19]=3[CH:20]=1)=[O:15])[CH2:6]2.N1CCCC1.[OH-].[Na+]>[Cu]I.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.C1COCC1>[N:5]12[CH2:12][CH2:11][CH:8]([CH2:9][CH2:10]1)[C@@H:7]([NH:13][C:14]([C:16]1[O:17][C:18]3[CH:24]=[C:23]([C:3]#[C:2][CH2:1][OH:4])[CH:22]=[CH:21][C:19]=3[CH:20]=1)=[O:15])[CH2:6]2

Participants

8

Reactant 4

HCID 7859Propargyl alcoholHCID 14798Sodium HydroxideHCID 31268PyrrolidineHCID 59341401N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-6-bromo-1-benzofuran-2-carboxamide

Product 1

HCID 58485659HCID 58485659, compound

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 289 mg (5.15 mmol) of propargyl alcohol, 150 mg (0.43 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-bromo-1-benzofuran-2-carboxamide (Example 2A), 1.6 mg (0.01 mmol) of copper(I) iodide, 15 mg (0.02 mmol) of bis(triphenylphosphine)palladium(II) chloride, 61 mg (0.86 mmol) of pyrrolidine and 1 ml of THF is heated under reflux overnight. The crude product is mixed with 10 ml of 1N sodium hydroxide solution and extracted three times with a total of 100 ml of ethyl acetate. The combined organic phases are dried over magnesium sulphate, and the solvent is removed under reduced pressure. The crude product is purified on silica gel 60 (Merck, Darmstadt; eluent: dichloromethane/triethylamine 100:1, then dichloromethane/methanol/triethylamine 100:1:1 to dichloromethane/methanol/triethylamine 100:10:1). The solvent is removed under reduced pressure. Finally, the last residues of solvent are removed under high vacuum. 40 mg (27% of theory) of the title compound are isolated.

Workup

  1. temperatureis heated
  2. temperatureunder reflux overnight
  3. extractionextracted three times with a total of 100 ml of ethyl acetate
  4. dry with materialThe combined organic phases are dried over magnesium sulphate
  5. customthe solvent is removed under reduced pressure
  6. customThe crude product is purified on silica gel 60 (Merck, Darmstadt
  7. customThe solvent is removed under reduced pressure
  8. customFinally, the last residues of solvent are removed under high vacuum

Sources & evidence

ORD record
ord-29faed2a361742479db13d1ba4fd6e85
Source dataset
uspto-grants-2011_07
Patent number
US07977485B2

Reaction notes

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