Hydrochloric Acid → HCID 91885084, compound

HRID 713378Notes

Reaction equation

HRID 713378 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][CH3:23])=[CH:17][CH:16]=3)=[CH:11][C:10]=2[F:24])[CH:5]=[C:6]([F:8])[CH:7]=1.C([Li])CCC.CCCCCC.B(OC)(OC)[O:37]C.Cl>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][CH3:23])=[CH:17][CH:16]=3)=[CH:11][C:10]=2[F:24])[CH:5]=[C:6]([F:8])[C:7]=1[OH:37]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8470Trimethyl borateHCID 595924131~3~,1~5~,2~2~-Trifluoro-3~4~-propyl-1~1~,2~1~:2~4~,3~1~-terphenylHCID 178418244HCID 178418244, compound

Product 1

HCID 91885084HCID 91885084, compoundYield 74.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

Under a nitrogen atmosphere, the 3,5-difluoro-[2-fluoro-4-(4-propylphenyl)phenyl]benzene (18.7 g) obtained in the process (1-1) was dissolved in THF (90 mL), and the solution was cooled to −40° C. or lower. Then, 1.6 mol/L of an n-butyllithium/hexane solution (40 mL) was added thereto at a rate which did not allow the internal temperature to be −35° C. or higher, and the product was stirred at −40° C. for an hour. Then, trimethyl borate (7.1 g) was added thereto at −40° C. at a rate which did not allow the internal temperature to be −35° C. or higher. The temperature was slowly increased to room temperature, the product was further stirred for 30 minutes at room temperature, 10% hydrochloric acid (50 mL) was subsequently added thereto under cooling with ice to separate the organic layer, and the organic layer was washed with a saturated salt solution. Then, a 30% hydrogen peroxide solution (8.4 g) was slowly added thereto, and then the product was stirred at 40° C. for 14 hours. The product was cooled with ice, and a 10% aqueous sodium sulfite solution was added thereto at a rate which did not allow the internal temperature to exceed 20° C., thereby separating the organic layer. Toluene was added to the water layer for extraction, the organic layer was added thereto and then washed with a saturated salt solution, and sodium sulfate was added thereto for dehydration. The solvent was distilled off under reduced pressure, and the product was purified by silica gel column chromatography and then recrystallized from hexane, thereby yielding 14.6 g of 2,6-difluoro-4-[2-fluoro-4-(4-propylphenyl)phenyl]phenol (A).

Workup

  1. customto be −35° C.
  2. customat −40° C.
  3. customto be −35° C.
  4. temperatureThe temperature was slowly increased to room temperature
  5. stirringthe product was further stirred for 30 minutes at room temperature
  6. temperatureunder cooling with ice
  7. customto separate the organic layer
  8. washthe organic layer was washed with a saturated salt solution
  9. additionThen, a 30% hydrogen peroxide solution (8.4 g) was slowly added
  10. stirringthe product was stirred at 40° C. for 14 hours
  11. temperatureThe product was cooled with ice
  12. additiona 10% aqueous sodium sulfite solution was added
  13. customto exceed 20° C.
  14. customseparating the organic layer
  15. additionToluene was added to the water layer for extraction
  16. additionthe organic layer was added
  17. washwashed with a saturated salt solution, and sodium sulfate
  18. additionwas added
  19. distillationThe solvent was distilled off under reduced pressure
  20. customthe product was purified by silica gel column chromatography
  21. customrecrystallized from hexane

Sources & evidence

ORD record
ord-7223774d1b1142dca53cb0b7103bf368
Source dataset
uspto-grants-2015_11
Patent number
US09181484B2

Reaction notes

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