Hydrochloric Acid → 3,3'-Difluoro-4-propoxybiphenyl

HRID 1530756Notes

Reaction equation

HRID 1530756 reaction equation
[F:1][C:2]1[CH:3]=[C:4](Br)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][CH2:10][CH3:11].OB(O)[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=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>[F:1][C:2]1[CH:3]=[C:4]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][CH2:10][CH3:11]

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 8470Trimethyl borateHCID 11430Potassium CarbonateHCID 140821-Bromo-3-fluorobenzeneHCID 27339863-Fluorophenylboronic acidHCID 5462224MagnesiumHCID 146182474-Bromo-2-fluoro-1-propoxybenzene

Product 1

HCID 212524043,3'-Difluoro-4-propoxybiphenylYield 86.1%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 22263336Toluene heptaneSolventHCID 86587398Ethanol toluene waterSolvent

Procedure

A mixture of 22.0 g (94.4 mmol) of 3-fluoro-4-propoxybromobenzene, 22.5 g (141.6 mmol) of dihydroxy(3-fluorophenyl)borane (prepared by reacting a Grignard reagent, which was prepared from 3-fluorobromobenzene and magnesium, with trimethoxyborane, and then hydrolysing with hydrochloric acid), 26.1 g (188.8 mmol) of K2CO3, 2.0 g of 5%Pd—C, and 150 ml of mixed solvent of toluene/ethanol/water (1/1/1) was heated to reflux for 27 hours. Subsequently, the Pd—C was removed by filtration, the mixture was extracted with 150 ml of toluene, 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=1/1) to obtain 20.1 g of a crude 3,3′-difluoro-4-propoxybiphenyl. (Yield: 86.1%)

Workup

  1. customprepared
  2. temperaturewas heated
  3. temperatureto reflux for 27 hours
  4. customSubsequently, the Pd—C was removed by filtration
  5. extractionthe mixture was extracted with 150 ml of toluene
  6. customthe organic layer thus obtained
  7. washwas washed with water thrice
  8. dry with materialdried over anhydrous magnesium sulfate
  9. distillationThe solvent was distilled off under a reduced pressure
  10. customthe residue thus obtained

Sources & evidence

ORD record
ord-8261f870b20b4cb68712e89c71310e11
Source dataset
uspto-grants-2001_03
Patent number
US06197217B1

Reaction notes

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