2-Bromothiazole → HCID 58438508, compound

HRID 1913407Notes

Reaction equation

HRID 1913407 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[C:14](=[O:18])[CH2:13][CH2:12]3)O1.Br[C:21]1[S:22][CH:23]=[CH:24][N:25]=1>COCCOC>[S:22]1[CH:23]=[CH:24][N:25]=[C:21]1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[C:14](=[O:18])[CH2:13][CH2:12]2

Participants

4

Reactant 2

HCID 764302-BromothiazoleHCID 185417105-(tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-one

Product 1

HCID 58438508HCID 58438508, compound

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)indan-1-one (SM-1a, 350 mg, 0.95 mmol) and 2-bromothiazole (156 mg, 0.95 mmol) were combined in DME (10 mL), and the mixture was purged with nitrogen for 10 minutes. Aqueous sodium carbonate solution (2M, 0.95 mL) and Pd(dppf)Cl2 (34 mg, 5 mol %) were added. The solution was purged with nitrogen for 10 minutes and was heated at reflux for 5 hours. The reaction was cooled and held at room temperature overnight. The reaction mixture was partitioned between ethyl acetate and water and separated. The aqueous layer was washed with 15 mL ethyl acetate (2×), and the combined organic portions were washed with brine and dried over MgSO4. Filtration and solvent removal afforded the crude product as a brown paste which was purified by silica chromatography on Combiflash ISCO purification system (Teledyne Corp., Lincoln Nebr.) eluting with a heptanes/ethyl acetate gradient. The final product was obtained as a light yellow flaky solid (SM-1f, 195 mg, 95%). MS (ES+) 216.2, 1H NMR (CDCl3) δ 2.72-2.75 (m, 2H), 3.20 (t, 2H), 7.42 (d, 1H), 7.80 (d, 1H), 7.92 (d, 1H), 7.94-7.97 (m, 1H), 8.10 (br s, 1H).

Workup

  1. customthe mixture was purged with nitrogen for 10 minutes
  2. additionAqueous sodium carbonate solution (2M, 0.95 mL) and Pd(dppf)Cl2 (34 mg, 5 mol %) were added
  3. customThe solution was purged with nitrogen for 10 minutes
  4. temperaturewas heated
  5. temperatureat reflux for 5 hours
  6. temperatureThe reaction was cooled
  7. customThe reaction mixture was partitioned between ethyl acetate and water
  8. customseparated
  9. washThe aqueous layer was washed with 15 mL ethyl acetate (2×)
  10. washthe combined organic portions were washed with brine
  11. dry with materialdried over MgSO4
  12. filtrationFiltration and solvent removal
  13. customafforded the crude product as a brown paste which
  14. customwas purified by silica chromatography on Combiflash ISCO purification system (Teledyne Corp., Lincoln Nebr.)
  15. washeluting with a heptanes/ethyl acetate gradient

Sources & evidence

ORD record
ord-fd8213cd119644ae830853e9b1651504
Source dataset
uspto-grants-2013_12
Patent number
US08609680B2

Reaction notes

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