Triethylamine → HCID 86590764, compound

HRID 1352592Notes

Reaction equation

HRID 1352592 reaction equation
C(N(CC)CC)C.Br[C:9]1[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=1.[CH2:15]([O:18][CH2:19][CH2:20][NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C:16]#[CH:17]>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>[N:11]1[CH:12]=[CH:13][CH:14]=[C:9]([C:17]#[C:16][CH2:15][O:18][CH2:19][CH2:20][NH:21][C:22](=[O:28])[O:23][C:24]([CH3:26])([CH3:25])[CH3:27])[CH:10]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 122863-BromopyridineHCID 21913902Carbamic acid, [2-(2-propynyloxy)ethyl]-, 1,1-dimethylethyl ester (9CI)

Product 1

HCID 86590764HCID 86590764, compoundYield 73.5%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
80 °C

Procedure

Under a nitrogen atmosphere, anhydrous triethylamine (45.5 mL, 326 mmol) and 3-bromopyridine (12.9 mL, 138 mmol) were added to a solution of tert-butyl 2-(prop-2-ynyloxy)ethylcarbamate (26.0 g, 125 mmol) in anhydrous DMF (400 mL), and the reaction was heated at 80° C. Dichlorobis(triphenylphosphine)palladium (II) (1.76 g, 2.51 mmol) and copper (I) iodide (0.96 g, 5.02 mmol) were then added, and the reaction was heated at 80° C. for one hour. The volatiles were removed under reduced pressure, and the residual black oil was dissolved in ethyl acetate (500 mL). The solution was washed with dilute aqueous sodium bicarbonate (1×200 mL) and brine (2×100 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to provide a dark brown oil. The oil was purified by column chromatography on silica gel (350 g, eluting with 50:50 ethyl acetate:hexane), and the resulting dark oil was dissolved in hot methanol (200 mL) and treated with 10 g of activated charcoal. The mixture was filtered through a layer of CELITE filter aid, and the filtrate was treated with additional activated charcoal (10 g) and filtered in the same way to provide 25.4 g of tert-butyl {2-[3-(pyridin-3-yl)prop-2-ynyloxy]ethyl}carbamate as a light amber-colored oil.

Workup

  1. temperaturethe reaction was heated at 80° C. for one hour
  2. customThe volatiles were removed under reduced pressure
  3. dissolutionthe residual black oil was dissolved in ethyl acetate (500 mL)
  4. washThe solution was washed with dilute aqueous sodium bicarbonate (1×200 mL) and brine (2×100 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto provide a dark brown oil
  9. customThe oil was purified by column chromatography on silica gel (350 g, eluting with 50:50 ethyl acetate:hexane)
  10. dissolutionthe resulting dark oil was dissolved in hot methanol (200 mL)
  11. additiontreated with 10 g of activated charcoal
  12. filtrationThe mixture was filtered through a layer of CELITE
  13. filtrationfilter aid
  14. additionthe filtrate was treated with additional activated charcoal (10 g)
  15. filtrationfiltered in the same way

Sources & evidence

ORD record
ord-e988c02bf3dd4137b7b3dcbecaec3b7c
Source dataset
uspto-grants-2007_05
Patent number
US07220758B2

Reaction notes

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