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

HRID 2219711Notes

Reaction equation

HRID 2219711 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-92c1bd0c2d724498ad1dd3d804db1377
Source dataset
uspto-grants-2008_08
Patent number
US07414071B2

Reaction notes

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