Hydrogen Bromide → 2-Bromo-4-trifluoromethyl-thiazole-5-carboxylic acid ethyl ester

HRID 2279649Notes

Reaction equation

HRID 2279649 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9](N)=[N:8][C:7]=1[C:12]([F:15])([F:14])[F:13])=[O:5])[CH3:2].N([O-])=O.[Na+].[BrH:20]>O>[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([Br:20])=[N:8][C:7]=1[C:12]([F:15])([F:14])[F:13])=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 260Hydrogen Bromide2×HCID 676565-Thiazolecarboxylic acid, 2-amino-4-(trifluoromethyl)-, ethyl esterHCID 23668193Sodium Nitrite

Product 1

HCID 132827592-Bromo-4-trifluoromethyl-thiazole-5-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 2-amino-4-trifluoromethyl-thiazole-5-carboxylic acid ethyl ester (10 g) in 48% HBr (75 mL) at 0° C. is added a solution of sodium nitrite (4.25 g) in water (50 mL) dropwise over 1 h. The mixture is stirred at the same temperature for an additional 30 min, then a solution of CuBr (6 g) in 48% HBr (50 mL) is added dropwise over 30 min. The reaction mixture is stirred for additional 30 min at 0° C. and for 2 h at RT. The mixture is extracted three times with methylene chloride. The combined organic extracts are dried over magnesium sulfate and concentrated in vacuo. The residue is purified by chromatography (silica gel, hexane to 3% EtOAc/Hexane) to yield the title compound.

Workup

  1. stirringThe reaction mixture is stirred for additional 30 min at 0° C. and for 2 h at RT
  2. extractionThe mixture is extracted three times with methylene chloride
  3. dry with materialThe combined organic extracts are dried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue is purified by chromatography (silica gel, hexane to 3% EtOAc/Hexane)

Sources & evidence

ORD record
ord-c5ba044b362242718645161adb21288b
Source dataset
uspto-grants-2015_09
Patent number
US09133204B2

Reaction notes

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