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

HRID 1823944Notes

Reaction equation

HRID 1823944 reaction equation
N[C:2]1[S:3][CH:4]=[C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[N:6]=1.[Br-:12].[Na+].S(=O)(=O)(O)O.[N+]([O-])([O-])=O.[Na+]>O.S([O-])([O-])(=O)=O.[Cu+2]>[Br:12][C:2]1[S:3][CH:4]=[C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[N:6]=1

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 24268Sodium NitrateHCID 73216Ethyl 2-aminothiazole-4-carboxylateHCID 253881Sodium Bromide

Product 1

HCID 353965Ethyl 2-bromo-1,3-thiazole-4-carboxylateYield 19.3%

Reagents, catalysts & solvents 2

HCID 24462Copper SulfateCatalystHCID 962WaterSolvent2×

Conditions

Temperature
0 °C

Procedure

Acording to literature reference (Kelly, T. R.; Lang, F. J. Org. Chem. 1996, 61, 4623–4633), crude ethyl 2-amino-4-thiazolecarboxylate (19.0 g, 111 mmol) is combined with sodium bromide (46.7 g, 444 mmol) and copper (II) sulfate (52.4 g, 333 mmol). A portion of 9N sulfuric acid (225 mL) is then added and the reaction mixture is cooled in an ice/salt bath. A solution of sodium nitrate (8.35 g, 122 mmol) in water (100 mL) is added drop wise to this reaction mixture over 30 minutes while maintaining the reaction temperature at 0° C. Once the addition is complete, the reaction mixture is stirred at 0° C. for 30 minutes and at 25° C. for an additional 1.5 hours. A portion of water (300 mL) is then added and the reaction mixture extracted with diethyl ether. Subsequently, the aqueous layer is made basic (pH 9) by addition of 20% sodium hydroxide and then extracted a second time with diethyl ether. The combined organic extracts are dried over sodium sulfate and concentrated. The crude product is purified by column chromatography (20% ethyl acetate in hexanes) to afford 5.06 g of ethyl 2-bromo-4-thiazolecarboxylate.

Workup

  1. temperaturethe reaction mixture is cooled in an ice/salt bath
  2. additionOnce the addition
  3. extractionthe reaction mixture extracted with diethyl ether
  4. additionby addition of 20% sodium hydroxide
  5. extractionextracted a second time with diethyl ether
  6. dry with materialThe combined organic extracts are dried over sodium sulfate
  7. concentrationconcentrated
  8. customThe crude product is purified by column chromatography (20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-fbb0a6b3355743dd93bcbb52df77197d
Source dataset
uspto-grants-2006_05
Patent number
US07041690B2

Reaction notes

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