Hydrochloric Acid → 4-Ethoxy-2,3,3'-trifluorobiphenyl

HRID 321899Notes

Reaction equation

HRID 321899 reaction equation
[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7](I)=[C:6]([F:11])[C:5]=1[F:12])[CH3:2].C(O[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[C:17]=1F)C.C([Li])(CC)C.II.OB(O)C1C=CC=C(F)C=1.FC1C=C(Br)C=CC=1.[Mg].COB(OC)OC.Cl.C([O-])([O-])=O.[K+].[K+]>[Pd].CCCCCCC.C1(C)C=CC=CC=1.C1(C)C=CC=CC=1.C(O)C.O>[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=2)=[C:6]([F:11])[C:5]=1[F:12])[CH3:2]

Participants

14

Reactant 10

HCID 313Hydrochloric AcidHCID 807IodineHCID 8470Trimethyl borateHCID 11430Potassium CarbonateHCID 140821-Bromo-3-fluorobenzeneHCID 27339863-Fluorophenylboronic acidHCID 27829281-Ethoxy-2,3-DifluorobenzeneHCID 5462224MagnesiumHCID 220080781-Ethoxy-2,3-difluoro-4-iodobenzeneHCID 178418400CID 53628100

Product 1

HCID 220080804-Ethoxy-2,3,3'-trifluorobiphenylYield 86.2%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 22263336Toluene heptaneSolventHCID 86587398Ethanol toluene waterSolvent

Procedure

Mixture of 20.0 g (79.3 mmol) of 4-ethoxy-2,3-difluoroiodobenzene [obtained by lithiating 4-ethoxy-2,3-difluorobenzene with sec-butyl lithium and then reacting with iodine], 18.9 g (118.9 mmol) of dihydroxy(3-fluorophenyl)borane [obtained by reacting a Grignard reagent, which was prepared from 3-fluorobromobenzene and magnesium, with trimethoxyborane and then hydrolyzing with hydrochloric acid], 21.9 g (158.6 mmol) of K2CO3, 2.0 g of 5% Pd—C, and 100 ml of mixed solvent of toluene/ethanol/ water (1/1/1) was heated to reflux for 13 hours. Subsequently, after the catalyst was filtered off, the mixture was subjected to extraction with toluene, and the organic layer thus obtained was washed with water thrice and then dried over anhydrous magnesium sulfate. The solvent was distilled off under a reduced pressure and the residue thus obtained was subjected to silica gel column chromatography (eluent: heptane/toluene=8/2) to obtain 17.3 g of a crude 4-ethoxy-2,3,3′-trifluorobiphenyl. (Yield: 86.2%)

Workup

  1. customobtained
  2. customobtained
  3. temperaturewas heated
  4. temperatureto reflux for 13 hours
  5. filtrationSubsequently, after the catalyst was filtered off
  6. extractionthe mixture was subjected to extraction with toluene
  7. customthe organic layer thus obtained
  8. washwas washed with water thrice
  9. dry with materialdried over anhydrous magnesium sulfate
  10. distillationThe solvent was distilled off under a reduced pressure
  11. customthe residue thus obtained

Sources & evidence

ORD record
ord-e423a5131e13433cac4e01965d820391
Source dataset
uspto-grants-2001_04
Patent number
US06210761B1

Reaction notes

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