Sulfuric Acid → Ethyl 2-bromo-1,3-thiazole-4-carboxylate

HRID 352608Notes

Reaction equation

HRID 352608 reaction equation
N([O-])=O.[Na+].[CH2:5]([O:7][C:8]([C:10]1[N:11]=[C:12](N)[S:13][CH:14]=1)=[O:9])[CH3:6].[Na+].[Br-:17].OS(O)(=O)=O.[OH-].[Na+]>O>[CH2:5]([O:7][C:8]([C:10]1[N:11]=[C:12]([Br:17])[S:13][CH:14]=1)=[O:9])[CH3:6]

Participants

7

Reactant 5

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 73216Ethyl 2-aminothiazole-4-carboxylateHCID 253881Sodium BromideHCID 23668193Sodium Nitrite

Product 1

HCID 353965Ethyl 2-bromo-1,3-thiazole-4-carboxylateYield 37.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
0 °C

Procedure

A cold solution of sodium nitrite (228 mg, 3.31 mmol) in water (2.0 mL) was added dropwise to a mixture of 2-amino-thiazole-4-carboxylic acid ethyl ester (J. Am. Chem. Soc., 1946, 68, 266) (500 mg, 2.90 mmol), CuSO4 pentahydrate (2.100 g, 8.41 mmol), NaBr (1.134 g, 11.02 mmol), H2SO4 (3.0 mL) and water (3.0 mL) at −5° C. to 0° C. The reaction mixture was stirred at 0° C. for 20 minutes and at room temperature for 1 h. The reaction mixture was adjusted to pH 9 with 1N NaOH (105 mL) and the aqueous solution was washed with CHCl3 (4×50 mL). The organic solutions were combined, dried (MgSO4), filtered and concentrated. Purification by medium pressure chromatography (39:1 hexanes:EtOAc to 19:1 hexanes:EtOAc) provided 2-bromo-thiazole-4-carboxylic acid ethyl ester (257 mg).

Workup

  1. washthe aqueous solution was washed with CHCl3 (4×50 mL)
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by medium pressure chromatography (39:1 hexanes:EtOAc to 19:1 hexanes:EtOAc)

Sources & evidence

ORD record
ord-9b27710e569e4c56a6ac9814590aa5eb
Source dataset
uspto-grants-2004_06
Patent number
US06747054B2

Reaction notes

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