Hydrogen Bromide → Ethyl 2-bromothiazole-5-carboxylate

HRID 1108286Notes

Reaction equation

HRID 1108286 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9](N)=[N:8][CH:7]=1)=[O:5])[CH3:2].[N+]([O-])(O)=O.N([O-])=O.[Na+].[BrH:20]>P(=O)(O)(O)O.O.[Cu]>[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([Br:20])=[N:8][CH:7]=1)=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 260Hydrogen BromideHCID 944Nitric AcidHCID 3146282-Amino-thiazole-5-carboxylic acid ethyl esterHCID 23668193Sodium Nitrite

Product 1

HCID 3614103Ethyl 2-bromothiazole-5-carboxylateYield 52%

Reagents, catalysts & solvents 3

HCID 23978CopperCatalystHCID 962WaterSolventHCID 1004Phosphoric AcidSolvent

Conditions

Temperature
-10 °C

Procedure

The starting material can be prepared as follows: To a 500 mL 24/40 3-neck round bottom flask equiped with a mechanical stirrer, was charged 3.4 g (19.7 mmol) of 2-amino-5-thiazolecarboxylic acid ethyl ester (Ber., 1888, 21, 938), partially dissolved in 30 mL of concentrated phosphoric acid. The stirring mixture was cooled in an ice bath and then 9 mL of concentrated nitric acid was added slowly, followed by the dropwise addition of 2.85 g (41.3 mmol) of sodium nitrite in 5 mL of water. The mixture was stirred in the cold for 35 minutes, and then added dropwise was 3.0 g (47.2 mmol) of copper powder in 75 mL of 48% hydrobromic acid cooled to -10° C. After the evolution of nitrogen gas ceased, the thick reaction mixture was removed from the ice bath and neutralized to pH 8, first using 5N sodium hydroxide and then sodium carbonate. The aqueous was then extracted with 400 mL ether. The insoluble material was filtered away and the filtrate was washed with 5% sodium bicarbonate, water, dried over sodium sulfate, and removed in vacuo. The crude residue was then purified using silica gel flash chromatography eluting with 1:1 ether/hexanes to give 2.4 g (52%) of 2-bromo-5-thiazolecarboxylic acid ethyl ester as a yellow oil. Rf =0.62 (1:1 ether/hexanes). 1H NMR (300 MHz, DMSO d6) δ 1.26 (t, J=7.0 Hz, 3H), 4.29 (q, J=7.1 Hz, 2H), 8.28 (s, 1H).

Workup

  1. customThe starting material can be prepared
  2. temperatureThe stirring mixture was cooled in an ice bath
  3. customthe thick reaction mixture was removed from the ice bath
  4. extractionThe aqueous was then extracted with 400 mL ether
  5. filtrationThe insoluble material was filtered away
  6. washthe filtrate was washed with 5% sodium bicarbonate, water
  7. dry with materialdried over sodium sulfate
  8. customremoved in vacuo
  9. customThe crude residue was then purified
  10. washeluting with 1:1 ether/hexanes

Sources & evidence

ORD record
ord-2c1281452df8492ca383fab51288a908
Source dataset
uspto-grants-2000_05
Patent number
US06066639

Reaction notes

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