Methyl iodide → Ethyl 2-[(tert-butoxycarbonyl)(methyl)amino]-1,3-thiazole-5-carboxylate

HRID 896472Notes

Reaction equation

HRID 896472 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([NH:10][C:11]1[S:12][C:13]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:14][N:15]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4].I[CH3:22].[OH-].[Na+]>C1COCC1.O>[C:3]([O:7][C:8]([N:10]([CH3:22])[C:11]1[S:12][C:13]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:14][N:15]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 7213140Ethyl 2-((tert-butoxy(hydroxy)methylidene)amino)-1,3-thiazole-5-carboxylate

Product 1

HCID 22350815Ethyl 2-[(tert-butoxycarbonyl)(methyl)amino]-1,3-thiazole-5-carboxylateYield 45%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A flask is charged with a suspension of sodium hydride (60% in mineral oil) (0.109 g, 2.72 mmol) in THF (5 mL). The ethyl 2-[(tert-butoxycarbonyl)amino]-1,3-thiazole-5-carboxylate (0.735 g, 2.70 mmol) is added, followed by iodomethane (175 μL, 2.70 mmol) and the resulting suspension is heated to reflux for 3 hr, then cooled to rt. Water is added, followed by 1.0 N NaOH. The basic phase is extracted with 3 portions of EtOAc. The combined organic phases are washed with brine, dried over Na2SO4, filtered, and concentrated to give a clear oil purified with flash chromatography to give ethyl 2-[(tert-butoxycarbonyl)(methyl)amino]-1,3-thiazole-5-carboxylate. Yield 45%. HRMS (FAB) calculated for C12H18N2O4S+H 287.1065, found 287.1068.

Workup

  1. temperaturethe resulting suspension is heated
  2. temperatureto reflux for 3 hr
  3. extractionThe basic phase is extracted with 3 portions of EtOAc
  4. washThe combined organic phases are washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a clear oil
  9. custompurified with flash chromatography

Sources & evidence

ORD record
ord-040786c4fce74c3cb0245e6768d946e4
Source dataset
uspto-grants-2005_07
Patent number
US06919359B2

Reaction notes

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