Methyl iodide → 5-Thiazolecarboxylic acid, 2-[methyl(tetrahydro-2H-pyran-2-yl)amino]-, ethyl ester

HRID 1188124Notes

Reaction equation

HRID 1188124 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[NH:7][C:8]1[S:9][C:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][N:12]=1.[H-].[Na+].[CH3:20]I>C1COCC1>[CH3:20][N:7]([CH:2]1[CH2:3][CH2:4][CH2:5][CH2:6][O:1]1)[C:8]1[S:9][C:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][N:12]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 43811197Ethyl 2-[(oxan-2-yl)amino]-1,3-thiazole-5-carboxylate

Product 1

HCID 594087635-Thiazolecarboxylic acid, 2-[methyl(tetrahydro-2H-pyran-2-yl)amino]-, ethyl esterYield 40.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Ethyl 2-(tetrahydro-2H-pyran-2-ylamino)thiazole-5-carboxylate (4.73 g, 18.5 mmol) was added to a suspension of NaH (740 mg, 18.5 mmol) in THF (20 mL) at 0° C., followed by methyl iodide (1.15 mL, 18.5 mmol). The resulting mixture was heated at reflux during 3 hrs. After quenching with water and extracting with AcOEt, the crude product was purified by column chromatography (50% AcOEt/PE), yielding ethyl 2-(methyl(tetrahydro-2H-pyran-2-yl)amino)thiazole-5-carboxylate (2.02 g, 40%) as an oil.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux during 3 hrs
  3. customAfter quenching with water
  4. extractionextracting with AcOEt
  5. customthe crude product was purified by column chromatography (50% AcOEt/PE)

Sources & evidence

ORD record
ord-805a7c1ba1cb4e3aa041f53828e48725
Source dataset
uspto-grants-2014_03
Patent number
US08673940B2

Reaction notes

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