1-Bromo-2-fluorobenzene → 5-(2-Fluorophenyl)pent-4-yn-1-ol

HRID 72103

Reaction equation

HRID 72103 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[F:8].[CH2:9]([OH:14])[CH2:10][CH2:11][C:12]#[CH:13]>C(#N)C.[Cu]I.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:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[C:13]#[C:12][CH2:11][CH2:10][CH2:9][OH:14]

Participants

6

Reactant 2

HCID 612591-Bromo-2-fluorobenzeneHCID 793464-Pentyn-1-ol

Product 1

HCID 866878565-(2-Fluorophenyl)pent-4-yn-1-ol

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

1-Bromo-2-fluorobenzene [1072-85-1] (3.0 g, 17 mmol, 1.0 equiv) and pent-4-yn-1-ol [5390-04-5] (2.3 mL, 25 mmol, 1.5 equiv) were dissolved in acetonitrile (40 mL). CuI (0.13 g, 0.68 mmol, 0.04 equiv) and TEA (3.4 mL, 25 mmol, 1.5 equiv) was added to the stirred solution followed by tetrakis(triphenylphosphine)palladium(0) (0.39 g, 0.34 mmol, 0.02 equiv). The solution was heated at reflux for 16 hours. The solution was cooled, filtered through Celite, the Celite pad rinsed with EtOAc and the solvent removed by rotoevaporation. Column chromatography (9:1 hexanes:ethyl acetate) of the residue afforded pure 5-(2-fluorophenyl)pent-4-yn-1-ol Intermediate 60 (1.3 g, 43%).

Workup

  1. temperatureThe solution was heated
  2. temperatureat reflux for 16 hours
  3. temperatureThe solution was cooled
  4. filtrationfiltered through Celite
  5. washthe Celite pad rinsed with EtOAc
  6. customthe solvent removed by rotoevaporation

Sources & evidence

ORD record
ord-aba1e866d2cd413daa1a31e8afd20c22
Source dataset
uspto-grants-2014_09
Patent number
US08828973B2

Linked notes

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