Azobisisobutyronitrile → 4-(Bromomethyl)-5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole

HRID 1767946Notes

Reaction equation

HRID 1767946 reaction equation
Cl.[CH3:2][C:3]1[N:4]=[C:5]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=2)[S:6][C:7]=1[CH3:8].C(N(CC)CC)C.[Br:26]N1C(=O)CCC1=O.N(C(C)(C)C#N)=NC(C)(C)C#N>C(OCC)(=O)C.O>[Br:26][CH2:2][C:3]1[N:4]=[C:5]([C:9]2[CH:10]=[CH:11][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:13][CH:14]=2)[S:6][C:7]=1[CH3:8]

Participants

7

Reactant 4

HCID 6547AzobisisobutyronitrileHCID 8471TriethylamineHCID 67184N-bromobutanimideHCID 236144994,5-Dimethyl-2-(4-trifluoromethyl-phenyl)-thiazole hydrochloride

Product 1

HCID 236145004-(Bromomethyl)-5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazoleYield 13.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

4,5-Dimethyl-2-(4-trifluoromethyl-phenyl)-thiazole hydrochloride (2.6 g, 8.9 mmol) was suspended in ethyl acetate and ice water. Triethylamine (1.2 ml, 8.9 mmol) was added, the organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine/ice water 1/1 dried over sodium sulfate and the solvent was removed under reduced pressure. The residue was dried in vacuo and dissolved in acetonitrile (30 ml) under an argon atmosphere. The solution was cooled to 0° C., N-bromosuccinimide (2.05 g, 11.5 mmol) and 2,2′-azobis(2-methylpropionitrile) (145 mg, 0.89 mmol) were added and the reaction mixture was stirred at ambient temperature for 14 h. Water was added and the formed precipitate was filtered off, washed with water and dried in vacuo to give yellow crystals. The crystals were purified by column chromatography (silica gel, n-heptane/dichloromethane) to give 385 mg (1.2 mmol, 13%) of the title compound as off-white crystals.

Workup

  1. customthe organic layer was separated
  2. extractionthe aqueous layer was extracted with ethyl acetate
  3. washThe combined organic layers were washed with brine/ice water 1/1
  4. dry with materialdried over sodium sulfate
  5. customthe solvent was removed under reduced pressure
  6. customThe residue was dried in vacuo
  7. dissolutiondissolved in acetonitrile (30 ml) under an argon atmosphere
  8. filtrationthe formed precipitate was filtered off
  9. washwashed with water
  10. customdried in vacuo
  11. customto give yellow crystals
  12. customThe crystals were purified by column chromatography (silica gel, n-heptane/dichloromethane)

Sources & evidence

ORD record
ord-82410eb407d643738572c6ca31d08561
Source dataset
uspto-grants-2007_06
Patent number
US07235572B2

Reaction notes

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