Ethanol → 2-Fluoro-6-(4-nonylphenyl)pyridine

HRID 395245Notes

Reaction equation

HRID 395245 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[N:3]=1.[CH2:9]([C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1)[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17].C(O)C.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([C:21]2[CH:20]=[CH:19][C:18]([CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])=[CH:23][CH:22]=2)[N:3]=1

Participants

8

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 6394382-Bromo-6-fluoropyridineHCID 4589192B-(4-Nonylphenyl)boronic acid

Product 1

HCID 181728412-Fluoro-6-(4-nonylphenyl)pyridineYield 91%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A solution of 232 mmol of 2-bromo-6-fluoropyridine in 400 ml of toluene is admixed with 290 mmol of 4-nonylphenylboronic acid, 200 ml of ethanol, a solution of 464 mmol of sodium carbonate in 200 ml of water and 2.3 mmol of tetrakis(triphenylphosphine)palladium(0) at room temperature. The mixture is heated at the boil for 3.5 h. After cooling, the phases are separated, the aqueous phase is extracted with dichloromethane and the combined organic phases are dried with magnesium sulfate. The solvents are removed under reduced pressure and the raw product is purified by column chromatography over silica gel 60 using n-heptane/dichloro-methane 1:1 as eluent and recrystallization from acetonitrile/acetone 5:1, giving 63 g (91%) of 2-fluoro-6-(4-nonylphenyl)pyridine.

Workup

  1. customat room temperature
  2. temperatureThe mixture is heated at the boil for 3.5 h
  3. temperatureAfter cooling
  4. customthe phases are separated
  5. extractionthe aqueous phase is extracted with dichloromethane
  6. dry with materialthe combined organic phases are dried with magnesium sulfate
  7. customThe solvents are removed under reduced pressure
  8. customthe raw product is purified by column chromatography over silica gel 60 using n-heptane/dichloro-methane 1:1 as eluent
  9. customrecrystallization from acetonitrile/acetone 5:1

Sources & evidence

ORD record
ord-04758e1162094b77bd5f1bb7eea7cb40
Source dataset
uspto-grants-2003_08
Patent number
US06605323B1

Reaction notes

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