Hydrochloric Acid → HCID 59596558, compound

HRID 2264954Notes

Reaction equation

HRID 2264954 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([F:9])[CH:3]=1.C([Li])CCC.Cl[Si:16]([CH3:19])([CH3:18])[CH3:17].Cl.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.O>[F:9][C:4]1[CH:3]=[C:2]([Si:16]([CH3:19])([CH3:18])[CH3:17])[CH:7]=[CH:6][C:5]=1[OH:8]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6397ChlorotrimethylsilaneHCID 2724141Tetrabutylammonium FluorideHCID 27249814-Bromo-2-fluorophenolHCID 178418339Butyllithium

Product 1

HCID 59596558HCID 59596558, compoundYield 100%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution 4-bromo-2-fluoro-phenol (75 g, 0.39 mol) in THF (750 mL) was cooled to −78° C. and treated dropwise with n-butyllithium (471 mL, 2.5M solution) over 1 hour keeping the internal temperature below −60° C. After stirring for a further 30 minutes the mixture was treated with chlorotrimethylsilane (128 g, 1.18 mol) in THF (150 mL) over 30 minutes keeping the internal temperature below −60° C. After the addition the mixture was allowed to warm to 0° C. over 40 minutes. The mixture was poured into 1M hydrochloric acid and the layers separated. The aqueous layer was extracted with diethyl ether (×2) and the combined organic layers were washed with water, brine, dried (MgSO4) and concentrated in vacuo to give a colourless liquid. The liquid was dissolved in THF (750 mL) and treated with tetrabutylammonium fluoride (393 mL, 1M solution in THF). After 5 minutes the solution was poured into water and the layers separated. The aqueous layer was extracted with diethyl ether (×2) and the combined organic layers washed with water, brine, dried (MgSO4) and evaporated to a straw-coloured oil. The oil was dissolved in DCM/cyclohexane (1:1, 500 mL) and stirred with silica (15 g) and filtered. The filtrate was evaporated to give the title compound as an oil which solidified on standing (72 g, 100% yield). 1H NMR (CDCl3) 7.04-6.92 (2H, m), 6.92-6.76 (1H, m), and 0.077 (9H, s).

Workup

  1. customthe internal temperature below −60° C
  2. customthe internal temperature below −60° C
  3. additionAfter the addition the mixture
  4. customthe layers separated
  5. extractionThe aqueous layer was extracted with diethyl ether (×2)
  6. washthe combined organic layers were washed with water, brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customto give a colourless liquid
  10. customthe layers separated
  11. extractionThe aqueous layer was extracted with diethyl ether (×2)
  12. washthe combined organic layers washed with water, brine
  13. dry with materialdried (MgSO4)
  14. customevaporated to a straw-coloured oil
  15. dissolutionThe oil was dissolved in DCM/cyclohexane (1:1, 500 mL)
  16. stirringstirred with silica (15 g)
  17. filtrationfiltered
  18. customThe filtrate was evaporated

Sources & evidence

ORD record
ord-8b55a34d521942fcb58c126840f868b5
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

Loading…