Ethyl bromopyruvate → 4-(4-Ethoxycarbonyl-thiazol-2-yl)-4-methyl-piperidine-1-carboxylic acid tert-butyl ester

HRID 1516483Notes

Reaction equation

HRID 1516483 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH3:17])([C:14](=[S:16])[NH2:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[CH2:19][C:20](=O)[C:21]([O:23][CH2:24][CH3:25])=[O:22]>CCO>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:14]2[S:16][CH:19]=[C:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[N:15]=2)([CH3:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 66144Ethyl bromopyruvateHCID 574733781,1-Dimethylethyl 4-(aminocarbonothioyl)-4-methyl-1-piperidinecarboxylate

Product 1

HCID 579868564-(4-Ethoxycarbonyl-thiazol-2-yl)-4-methyl-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 4-methyl-4-thiocarbamoyl-piperidine-1-carboxylic acid tert-butyl ester (1 g, 4 mmol) in EtOH (10 mL) was added ethyl bromopyruvate (0.78 g, 4 mmol) at room temperature. The mixture was heated to refluxing for 3 hours. After cooling to room temperature, the solvent was removed in vacuo. The residue was dissolved in methylene chloride (15 mL), Et3N (1 mL) and di-tert-butyl dicarbonate (1.3 g) were added to the solution. The mixture was stirred at room temperature overnight. The mixture was washed with H2O and brine. After drying (Na2SO4), the solvent was removed in vacuo, and the residue was purified by silica column chromatography with EtOAc/hexanes to afford the desired product.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto refluxing for 3 hours
  3. customthe solvent was removed in vacuo
  4. dissolutionThe residue was dissolved in methylene chloride (15 mL)
  5. additionEt3N (1 mL) and di-tert-butyl dicarbonate (1.3 g) were added to the solution
  6. washThe mixture was washed with H2O and brine
  7. dry with materialAfter drying (Na2SO4)
  8. customthe solvent was removed in vacuo
  9. customthe residue was purified by silica column chromatography with EtOAc/hexanes

Sources & evidence

ORD record
ord-5b6fd1083ca94fe7b729b1acfe006c67
Source dataset
uspto-grants-2012_07
Patent number
US08227495B2

Reaction notes

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