Propyne → (6-Phenyl-4-prop-1-ynylpyridin-3-yl)carbamic acid tert-butyl ester

HRID 400604Notes

Reaction equation

HRID 400604 reaction equation
[CH:1]#[C:2][CH3:3].[C:4]([O:8][C:9](=[O:24])[NH:10][C:11]1[CH:12]=[N:13][C:14]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:15][C:16]=1I)([CH3:7])([CH3:6])[CH3:5].C(OCC)(=O)C.[Cl-].[NH4+]>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>[C:4]([O:8][C:9](=[O:24])[NH:10][C:11]1[CH:12]=[N:13][C:14]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:15][C:16]=1[C:1]#[C:2][CH3:3])([CH3:7])([CH3:6])[CH3:5]

Participants

9

Reactant 4

HCID 6335PropyneHCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 50999073Tert-butyl 4-iodo-6-phenylpyridin-3-ylcarbamate

Product 1

HCID 60026785(6-Phenyl-4-prop-1-ynylpyridin-3-yl)carbamic acid tert-butyl esterYield 96%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Propyne (0.60 mL, 11.4 mmol) was condensed in a pressure tube at −78° C. A solution of (4-iodo-6-phenylpyridin-3-yl)carbamic acid tert-butyl ester (900 mg, 2.27 mmol) in 2 mL of DMF, 6 mL of triethylamine, dichlorobis(triphenylphosphine)palladium (II) (80.2 mg, 0.114 mmol), and CuI (43.0 mg, 0.227 mmol) were added, the tube was sealed, and the mixture was stirred at room temperature overnight. The mixture was cooled to −78° C., the sealed tube was opened, and 20 mL of ethyl acetate and 10 mL of saturated aqueous ammonium chloride solution were added. The phases were separated and the aqueous layer was extracted with three 10 mL portions of ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude product was purified on SiO2 (0 to 40% ethyl acetate in hexanes, gradient) to give 670 mg of (6-phenyl-4-prop-1-ynylpyridin-3-yl)carbamic acid tert-butyl ester (96% yield).

Workup

  1. customcondensed in a pressure tube at −78° C
  2. customthe tube was sealed
  3. temperatureThe mixture was cooled to −78° C.
  4. customThe phases were separated
  5. extractionthe aqueous layer was extracted with three 10 mL portions of ethyl acetate
  6. dry with materialThe combined organic layers were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified on SiO2 (0 to 40% ethyl acetate in hexanes, gradient)

Sources & evidence

ORD record
ord-380cea053f37497091aef584cfc0eb28
Source dataset
uspto-grants-2014_06
Patent number
US08741897B2

Reaction notes

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