Methyl iodide → Tert-butyl 4-(2-(methyl(thiazol-2-yl)amino)-2-oxoethyl)piperazine-1-carboxylate

HRID 416823Notes

Reaction equation

HRID 416823 reaction equation
[O:1]=[C:2]([NH:17][C:18]1[S:19][CH:20]=[CH:21][N:22]=1)[CH2:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1.[H-].[Na+].[CH3:25]I>CN(C=O)C>[CH3:25][N:17]([C:18]1[S:19][CH:20]=[CH:21][N:22]=1)[C:2](=[O:1])[CH2:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:14])[CH3:15])=[O:11])[CH2:6][CH2:5]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 55591093tert-Butyl 4-(2-oxo-2-(thiazol-2-ylamino)ethyl)piperazine-1-carboxylate

Product 1

HCID 57897201Tert-butyl 4-(2-(methyl(thiazol-2-yl)amino)-2-oxoethyl)piperazine-1-carboxylateYield 62.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of tert-butyl 4-(2-oxo-2-(thiazol-2-ylamino)ethyl)piperazine-1-carboxylate (0.056 g, 0.17 mmol) in anhydrous DMF (1.0 mL) cooled into an ice-bath under argon was added sodium hydride (60% dispersion; 7.8 mg, 0.19 mmol). Stirring was continued at 0° C. for ˜2 min and then methyl iodide (0.048 g, 0.34 mmol) was added with the aid of DMF (0.4 mL), the reaction mixture was stirred for 1.5 h under argon, and then partitioned between ethyl acetate (30 mL) and brine (30 mL). The aqueous layer was extracted with ethyl acetate (30 mL), and the combined organics were washed with brine (2×30 mL), dried (Na2SO4), and concentrated in vacuo. Purification by chromatography (10 g isolute column, 80% ethyl acetate in petroleum ether 60-80° C.) afforded the title compound as an oil (0.036 g, 62%); 1H-NMR (500 MHz, DMSO-d6) 1.40 (s, 9H, C(CH3)3), 3.33 (s, 4H, piperazine N(CH2)2), 3.58 (s, 2H, NCH2CO), 3.68 (s, 3H, CH3), 7.27 (d, J=3.5 Hz, 1H, thiazole H), 7.53 (d, J=3.5 Hz, 1H, thiazole H);

Workup

  1. stirringthe reaction mixture was stirred for 1.5 h under argon
  2. custompartitioned between ethyl acetate (30 mL) and brine (30 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (30 mL)
  4. washthe combined organics were washed with brine (2×30 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customPurification by chromatography (10 g isolute column, 80% ethyl acetate in petroleum ether 60-80° C.)

Sources & evidence

ORD record
ord-f2c959131dcd4ec39cee4d1514c09726
Source dataset
uspto-grants-2012_01
Patent number
US08088761B2

Reaction notes

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