Triethylamine → benzyl 5-(1H-imidazol-5-yl)pent-4-ynoate

HRID 870582Notes

Reaction equation

HRID 870582 reaction equation
I[C:2]1[N:3]=[CH:4][NH:5][CH:6]=1.[C:7]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)(=[O:12])[CH2:8][CH2:9][C:10]#[CH:11].C(N(CC)CC)C>CN(C)C=O.O.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>[NH:3]1[C:2]([C:11]#[C:10][CH2:9][CH2:8][C:7]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:12])=[CH:6][N:5]=[CH:4]1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 561097Benzyl 4-pentynoateHCID 178506559HCID 178506559, compound

Product 1

HCID 86726543benzyl 5-(1H-imidazol-5-yl)pent-4-ynoateYield 69%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

Add bis(triphenylphosphine)palladium(II) chloride (0.14 g; 0.1 equiv; 0.20 mmoles) and copper(I) iodide (0.039 mg; 0.1 equiv; 0.20 mmoles) to a deoxygenated solution of 4-iodo-1H-imidazole (0.388 g; 1.0 equiv; 2.00 mmoles), benzyl pent-4-ynoate (0.376 g; 1.0 equiv; 2.00 mmoles), and triethylamine (0.84 mL; 3 equiv; 6.0 mmoles) in dimethylformamide (8 mL). Heat the mixture to 75° C. for 16 hours, then dilute the mixture with water (30 mL) and extract 3× with ethyl acetate. Wash the combined organic extracts with brine, dry over magnesium sulfate, filter, and concentrate to provide the crude product. Purify the crude product by column chromatography (0 to 10% methanol in dichloromethane) to afford benzyl 5-(1H-imidazol-5-yl)pent-4-ynoate (0.35 g; 69%) as a colorless oil: MS (m/z): 255(M+1).

Workup

  1. extractionextract 3× with ethyl acetate
  2. washWash the combined organic extracts with brine
  3. dry with materialdry over magnesium sulfate
  4. filtrationfilter
  5. concentrationconcentrate
  6. customto provide the crude product
  7. customPurify the crude product by column chromatography (0 to 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-155eecd8ed134ae3b01bebfc5ff72213
Source dataset
uspto-grants-2015_03
Patent number
US08969555B2

Reaction notes

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