Sodium hydride → N-[5-chloro-3-(2-methoxyethyl)-1,3-thiazol-2(3H)-ylidene]acetamide

HRID 78460Notes

Reaction equation

HRID 78460 reaction equation
[C:1]([NH:4][C:5]1[S:6][C:7]([Cl:10])=[CH:8][N:9]=1)(=[O:3])[CH3:2].[H-].[Na+].[CH3:13][O:14][CH2:15][CH2:16]Br>C1COCC1.CN(C=O)C.C(OCC)(=O)C>[Cl:10][C:7]1[S:6][C:5](=[N:4][C:1](=[O:3])[CH3:2])[N:9]([CH2:16][CH2:15][O:14][CH3:13])[CH:8]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 809722-Bromoethyl methyl etherHCID 46841342-Acetamido-5-chlorothiazole

Product 1

HCID 66858991N-[5-chloro-3-(2-methoxyethyl)-1,3-thiazol-2(3H)-ylidene]acetamideYield 42%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

A flask was charged with 2-acetamido-5-chlorothiazole (Lancaster, 19.3 g, 110 mmol) in 200 mL of 2:1 THF/DMF. To the solution was added sodium hydride (60% dispersion in mineral oil, 5.44 g, 142 mmol). The mixture was stirred at room temperature for 15 min and then 2-bromoethyl methyl ether (18.3 g, 131 mmol) was added. The reaction mixture was warmed to 85° C. and stirred overnight. After cooling to room temperature, the mixture was diluted with ethyl acetate and washed with water. The organic extract was dried (MgSO4), filtered, and concentrated. The residue was purified by flash chromatography on SiO2 using a gradient of 0% to 100% ethyl acetate:hexane to provide 10.3 g (42%) of the title compound as the more polar regioisomer: 1H NMR (300 MHz, CDCl3) δ 2.28 (s, 3H) 3.35 (s, 3H) 3.65-3.71 (m, 2H) 4.28-4.36 (m, 2H) 7.00 (s, 1H); MS (ESI+) m/z 235 (M+H)+.

Workup

  1. temperatureThe reaction mixture was warmed to 85° C.
  2. stirringstirred overnight
  3. temperatureAfter cooling to room temperature
  4. washwashed with water
  5. extractionThe organic extract
  6. dry with materialwas dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography on SiO2 using a gradient of 0% to 100% ethyl acetate

Sources & evidence

ORD record
ord-0c07fa4fe393463390cb977460b50c84
Source dataset
uspto-grants-2014_09
Patent number
US08841334B2

Reaction notes

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