Methyl iodide → tert-Butyl {5-[{2-([tert-butoxycarbonyl)(methyl)amino]ethyl}(methyl)carbamoyl]-4-methylthiophen-2-yl}methylcarbamate

HRID 446588Notes

Reaction equation

HRID 446588 reaction equation
[H-].[Na+].C(OC(N[C:11]1[S:15][C:14]([C:16]([N:18]([CH3:30])[CH2:19][CH2:20][N:21]([CH3:29])[C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:17])=[C:13]([CH3:31])[CH:12]=1)=O)(C)(C)C.CI>CN(C)C=O.C(OCC)(=O)C>[C:24]([O:23][C:22]([N:21]([CH3:29])[CH2:20][CH2:19][N:18]([CH3:30])[C:16]([C:14]1[S:15][C:11]([CH2:20][NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:12][C:13]=1[CH3:31])=[O:17])=[O:28])([CH3:25])([CH3:26])[CH3:27]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86663470tert-Butyl {2-[({5-[(tert-butoxycarbonyl)amino]-3-methylthiophen-2-yl}carbonyl)(methyl)amino]ethyl}methylcarbamate

Product 1

HCID 86663472tert-Butyl {5-[{2-([tert-butoxycarbonyl)(methyl)amino]ethyl}(methyl)carbamoyl]-4-methylthiophen-2-yl}methylcarbamateYield 198.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Sodium hydride (50 mg, 55%, 1.14 mmol) was added to a solution of the compound (407 mg, 0.952 mmol) obtained in Example 89b in N,N-dimethylformamide (3 mL) under ice cooling, and the mixture was stirred at room temperature for 30 minutes. Methyl iodide (0.119 mL, 1.90 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature for 2.5 hours. The reaction mixture was diluted with ethyl acetate, and the organic layer was washed successively with water (×3) and saturated sodium chloride solution. The organic layer was dried with anhydrous sodium sulfate, then the solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1, v/v) to give the title compound (418 mg; yield, 99%) as a white solid.

Workup

  1. stirringthe mixture was stirred at room temperature for 2.5 hours
  2. washthe organic layer was washed successively with water (×3) and saturated sodium chloride solution
  3. dry with materialThe organic layer was dried with anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customthe resulting residue was purified by silica gel column chromatography (hexane

Sources & evidence

ORD record
ord-cca92d50428c4462a908de5a5512cf3c
Source dataset
uspto-grants-2013_07
Patent number
US08476253B2

Reaction notes

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