Tert-Butyl nitrite → Methyl 2-chloro-5-iodo-1,3-thiazole-4-carboxylate

HRID 1518274Notes

Reaction equation

HRID 1518274 reaction equation
N[C:2]1[S:3][C:4]([I:11])=[C:5]([C:7]([O:9][CH3:10])=[O:8])[N:6]=1.N(OC(C)(C)C)=O.[NH4+].[Cl-:20]>C(#N)C.Cl[Cu]>[Cl:20][C:2]1[S:3][C:4]([I:11])=[C:5]([C:7]([O:9][CH3:10])=[O:8])[N:6]=1

Participants

6

Reactant 3

HCID 10906Tert-Butyl nitriteHCID 25517Ammonium ChlorideHCID 59447673HCID 59447673, compound

Product 1

HCID 59447499Methyl 2-chloro-5-iodo-1,3-thiazole-4-carboxylateYield 78%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 6342AcetonitrileSolvent

Procedure

To a solution of methyl 2-amino-5-iodothiazole-4-carboxylate (8A) (9 g, 31.7 mmol) in acetonitrile (60 mL) was added CuCl (4.75 g, 48 mmol) followed by t-butyl nitrite (6.19 g, 60 mmol). The mixture was stirred at rt for 2 hours. NH4Cl was then added slowly to the stirring mixture to quench the reaction. The mixture was extracted with EtOAc and the combined extracts were washed with water, brine, dried over Na2SO4, and concentrated under reduced pressure. The crude material was purified by column chromatography on silica gel eluting with 5% EtOAc in hexanes to provide 7.5 g (78%) of the desired product methyl 2-chloro-5-iodothiazole-4-carboxylate (88): LC/MS (APCI): m/z 304.0 (M+H).

Workup

  1. customto quench
  2. customthe reaction
  3. extractionThe mixture was extracted with EtOAc
  4. washthe combined extracts were washed with water, brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified by column chromatography on silica gel eluting with 5% EtOAc in hexanes

Sources & evidence

ORD record
ord-b0a77555b5a34d31b21e846ed1e03d6e
Source dataset
uspto-grants-2012_07
Patent number
US08232273B2

Reaction notes

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