Hydrochloric Acid → 4-Ethoxycarbonyl-5-(2-trimethylsilylethynyl)thiazole

HRID 1799671Notes

Reaction equation

HRID 1799671 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[CH:8][S:9][C:10]=1I)=[O:5])[CH3:2].C(N(CC)CC)C.[C:19]([Si:21]([CH3:24])([CH3:23])[CH3:22])#[CH:20].Cl>CN(C=O)C.[Cl-].[Na+].O.[Cu]I.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OCC)(=O)C>[CH3:22][Si:21]([CH3:24])([CH3:23])[C:19]#[C:20][C:10]1[S:9][CH:8]=[N:7][C:6]=1[C:4]([O:3][CH2:1][CH3:2])=[O:5]

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 59705069Ethyl 5-iodothiazole-4-carboxylate

Product 1

HCID 592179544-Ethoxycarbonyl-5-(2-trimethylsilylethynyl)thiazole

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
60 °C

Procedure

4-Ethoxycarbonyl-5-iodothiazole (71.47 g) was dissolved in 250 ml of DMF. Triethylamine (70 ml), 53.4 ml of ethynyltrimethylsilane, 960 mg of copper(I) iodide, and 3.54 g of bis(triphenylphosphine) palladium(II) dichloride were added in that order, and the mixture was stirred at 60° C. under an argon atmosphere for 1.5 hr. The reaction solution was added to 1000 ml of ethyl acetate and 500 ml of brine. The mixture was adjusted to pH 3 by the addition of 1 N aqueous hydrochloric acid. The organic layer was separated and was washed with 500 ml of sodium bicarbonate water and 500 ml of brine in that order. The organic layer was dried over anhydrous magnesium sulfate, was filtered, and was concentrated under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=4:1 to 3:1) to give 53.66 g of 5-(2-trimethylsilylethynyl)-4-ethoxycarbonylthiazole. This product was dissolved in 250 ml of methanol, 3.1 of potassium carbonate was added to the solution under ice cooling, and the mixture was stirred at the same temperature for 45 min. The reaction solution was added to 500 ml of ethyl acetate and 250 ml of brine. The organic layer was separated and was washed twice with 500 ml of brine. The organic layer was dried over anhydrous magnesium sulfate, was filtered, and was concentrated under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=2:1 to 1:1) to give 29.91 g of 5-ethynyl-4-methoxycarbonylthiazole.

Workup

  1. customThe organic layer was separated
  2. washwas washed with 500 ml of sodium bicarbonate water and 500 ml of brine in that order
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. filtrationwas filtered
  5. concentrationwas concentrated under the reduced pressure
  6. customThe residue was purified by column chromatography on silica gel (hexane:ethyl acetate=4:1 to 3:1)

Sources & evidence

ORD record
ord-4bc444aadfcf43e08ff8d12c1ba2d22f
Source dataset
uspto-grants-2013_01
Patent number
US08344154B2

Reaction notes

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