Ethyl Acetate → 2-Amino-4-ethoxycarbonyl-5-ethynylthiazole

HRID 1799687Notes

Reaction equation

HRID 1799687 reaction equation
[NH2:1][C:2]1[S:3][C:4](I)=[C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[N:6]=1.[CH2:13]([Sn](CCCC)(CCCC)C#C)[CH2:14]CC.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.C(OCC)(=O)C>CN1CCCC1=O.[Cl-].[Na+].O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[Cl-].[Zn+2].[Cl-]>[NH2:1][C:2]1[S:3][C:4]([C:13]#[CH:14])=[C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[N:6]=1

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 521585Tris(furan-2-yl)phosphaneHCID 621176EthynyltributyltinHCID 45117588Ethyl 2-amino-5-iodo-1,3-thiazole-4-carboxylate

Product 1

HCID 866098122-Amino-4-ethoxycarbonyl-5-ethynylthiazole

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 13387N-methyl-2-pyrrolidoneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

2-Amino-4-ethoxycarbonyl-5-iodothiazole (1.40 g) prepared in step a) in Example 1 was dissolved in 20 ml of N-methyl-2-pyrrolidinone. tri-n-butylethynyltin (1.63 ml), 127 mg of tri(2-furyl)phosphine, 127 mg of tris(dibenzylideneacetone)dipalladium(0), and 1.27 g of zinc chloride were added to the solution under an argon atmosphere, and the mixture was stirred at room temperature for 2.5 hr. Brine and ethyl acetate were added to the reaction solution. The insolubles were removed by filtration through Celite, and the filtrate was extracted twice with ethyl acetate. The organic layers were combined, were washed with brine, were dried over anhydrous magnesium sulfate, were filtered, and were concentrated under the reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=3:1) to give 597 mg of 2-amino-4-ethoxycarbonyl-5-ethynylthiazole.

Workup

  1. customThe insolubles were removed by filtration through Celite
  2. extractionthe filtrate was extracted twice with ethyl acetate
  3. washwere washed with brine
  4. dry with materialwere dried over anhydrous magnesium sulfate
  5. filtrationwere filtered
  6. concentrationwere concentrated under the reduced pressure
  7. customThe residue was purified by column chromatography on silica gel (hexane:ethyl acetate=3:1)

Sources & evidence

ORD record
ord-88722b7372174981a37f44e11218b378
Source dataset
uspto-grants-2013_01
Patent number
US08344154B2

Reaction notes

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