Chlorotrimethylsilane → HCID 71150651, compound

HRID 407203Notes

Reaction equation

HRID 407203 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[Br:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[C:15]=1[F:21].[CH3:22][Si:23](Cl)([CH3:25])[CH3:24]>O1CCCC1>[Br:13][C:14]1[CH:19]=[CH:18][C:17]([Si:23]([CH3:25])([CH3:24])[CH3:22])=[C:16]([F:20])[C:15]=1[F:21]

Participants

6

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 7912DiisopropylamineHCID 27332601-Bromo-2,3-difluorobenzeneHCID 178418339Butyllithium

Product 1

HCID 71150651HCID 71150651, compoundYield 21.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-75 °C

Procedure

Diisopropylamine (7.86 grams (g), 78 mmol) was dissolved in tetrahydrofuran (THF; 104 mL) and cooled to −75° C. utilizing a dry ice/acetone bath. A solution of n-BuLi (2.5 M in hexanes; 22.80 mL, 57.0 mmol) was added dropwise, and the solution was again cooled to −75° C. 1-Bromo-2,3-difluorobenzene (10 g, 51.8 mmol) was dissolved in THF (25.9 mL), and the solution was added dropwise keeping the temperature below −60° C. The reaction mixture was then allowed to warm to −15° C. before cooling again to −75° C. TMSCl (7.29 mL, 57.0 mmol) was then added dropwise, and the reaction mixture was allowed to warm to 25° C. and then concentrated under vacuum. The residue was partitioned between ethyl acetate (EtOAc) and H2O. The organic phase was washed twice more with H2O and concentrated. Kugelrohr distillation at 88° C. provided the product in greater purity but an impurity was distilling at that temperature. Kugelrohr distillation of that purified distillate at 75° C. led to purer product but some product was left in the pot. This process yielded the title compound as a clear oil (3.0 g, 21.83%, 90% purity): 1H NMR (300 MHz, CDCl3) δ 7.28 (ddd, J=7.8, 5.2, 1.3 Hz, 1H), 6.98 (ddd, J=8.0, 4.8, 1.9 Hz, 1H), 0.32 (s, 9H); EIMS m/z 264, 266.

Workup

  1. temperaturethe solution was again cooled to −75° C
  2. additionthe solution was added dropwise
  3. customthe temperature below −60° C
  4. temperatureto warm to −15° C.
  5. temperaturebefore cooling again to −75° C
  6. temperatureto warm to 25° C.
  7. concentrationconcentrated under vacuum
  8. customThe residue was partitioned between ethyl acetate (EtOAc) and H2O
  9. washThe organic phase was washed twice more with H2O
  10. concentrationconcentrated
  11. distillationKugelrohr distillation at 88° C.
  12. customprovided the product in greater purity
  13. distillationan impurity was distilling at that temperature
  14. distillationKugelrohr distillation of that purified distillate at 75° C.
  15. waitsome product was left in the pot

Sources & evidence

ORD record
ord-49ac7209b7af46c4a7934c5b1c247b0c
Source dataset
uspto-grants-2014_06
Patent number
US08754229B2

Reaction notes

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