Peracetic Acid → 3-Bromo-6-chloro-2-fluorophenol

HRID 1398467Notes

Reaction equation

HRID 1398467 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[F:9].[Li+].CC([N-]C(C)C)C.B(OC)(OC)[O:19]C.C(OO)(=O)C>O1CCCC1>[Br:1][C:2]1[C:3]([F:9])=[C:4]([OH:19])[C:5]([Cl:8])=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6585Peracetic AcidHCID 8470Trimethyl borateHCID 1372751-Bromo-4-chloro-2-fluorobenzeneHCID 2724682Lithium diisopropylamide

Product 1

HCID 666010023-Bromo-6-chloro-2-fluorophenolYield 76.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

To a stirred solution of 1-bromo-4-chloro-2-fluorobenzene (5 g, 23.87 mmol) in tetrahydrofuran (40 mL) cooled to −78° C. was added LDA (14.92 mL, 29.8 mmol) dropwise. The reaction mixture was stirred at this temperature for 30 min. then allowed to warm to −20° C. and stirred for 30 min. The reaction was then cooled to −78° C. and trimethyl borate (3.47 mL, 31.0 mmol) dissolved in THF (5 mL) was added dropwise. The reaction mixture was warmed to −20° C. and stirred for 1 h. The reaction mixture was then cooled to −78° C. and peracetic acid (16 mL, 84 mmol) as slowly added dropwise. The mixture was allowed to warm to rt and stirred for 12 h. The reaction mixture was again cooled to 0° C. and quenched with 5% ammonium chloride The solution was extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with brine (50 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to afford 3-bromo-6-chloro-2-fluorophenol (4.99 g, 18.25 mmol, 76% crude yield) as a yellow oil. The material was carried forward without further purification. LC/MS (ESI) m/e 225.1 [(M+H)+, calcd for C6H4BrClFO 224.9]; LC/MS retention time (method E): tR=0.87 min.

Workup

  1. stirringstirred for 30 min
  2. temperatureThe reaction was then cooled to −78° C.
  3. additionwas added dropwise
  4. temperatureThe reaction mixture was warmed to −20° C.
  5. stirringstirred for 1 h
  6. temperatureThe reaction mixture was then cooled to −78° C.
  7. temperatureto warm to rt
  8. stirringstirred for 12 h
  9. temperatureThe reaction mixture was again cooled to 0° C.
  10. customquenched with 5% ammonium chloride The solution
  11. extractionwas extracted with ethyl acetate (2×50 mL)
  12. washThe combined organic layers were washed with brine (50 mL)
  13. dry with materialdried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-4617551a4f1845fa85ba6d578f926ecf
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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