Water → Ethyl 5-(3-methoxyprop-1-ynyl)-2-phenylthiazole-4-carboxylate

HRID 1799108Notes

Reaction equation

HRID 1799108 reaction equation
Br[C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[C:13]([O:15][CH2:16][CH3:17])=[O:14].[CH2:18]([O:21][CH3:22])[C:19]#[CH:20].O>C(COC)OC.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>[CH3:22][O:21][CH2:18][C:19]#[C:20][C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[C:13]([O:15][CH2:16][CH3:17])=[O:14]

Participants

7

Reactant 3

HCID 962WaterHCID 693933-MethoxypropyneHCID 44558337Ethyl 5-bromo-2-phenylthiazole-4-carboxylate

Product 1

HCID 67425118Ethyl 5-(3-methoxyprop-1-ynyl)-2-phenylthiazole-4-carboxylateYield 88%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

Nitrogen was bubbled through a solution of Ethyl 5-bromo-2-phenylthiazole-4-carboxylate (13.1 g, 41.9 mmol) and methyl propargyl ether (7.1 mL, 83.9 mmol) in dimethoxyethane (DME) (200 mL). Dichlorobis(triphenylphosphine)palladium (II) (1.47 g, 2.2 mmol), copper (I) iodide (0.2 g, 1.1 mmol), and TEA (29 mL, 210 mmol) were added and the reaction mixture was heated at reflux for 16 h. The reaction mixture was cooled to room temperature, poured into H2O (200 mL) and extracted with EtOAc (2×200 mL). The combined organics were washed with brine, dried (MgSO4), and concentrated. The crude product was purified by MPLC eluting with pentane/EtOAc (0-50% gradient) to give ethyl 5-(3-methoxyprop-1-ynyl)-2-phenylthiazole-4-carboxylate as a tan solid (11 g, 88% yield).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 16 h
  3. extractionextracted with EtOAc (2×200 mL)
  4. washThe combined organics were washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customThe crude product was purified by MPLC
  8. washeluting with pentane/EtOAc (0-50% gradient)

Sources & evidence

ORD record
ord-777aa7626cef49af9c9c8d2565fc433f
Source dataset
uspto-grants-2013_01
Patent number
US08343997B2

Reaction notes

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