Hydrochloric Acid → 1-(2-Fluoro-3-hexyloxyphenyl)ethyne

HRID 1018405Notes

Reaction equation

HRID 1018405 reaction equation
Br[C:2]1[C:7]([F:8])=[C:6]([O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH:5]=[CH:4][CH:3]=1.[CH3:16][C:17](O)(C#C)C.Cl>C(N(CC)CC)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu](I)I>[F:8][C:7]1[C:6]([O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])=[CH:5][CH:4]=[CH:3][C:2]=1[C:16]#[CH:17]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 82582-Methyl-3-butyn-2-olHCID 18401260HCID 18401260, compound

Product 1

HCID 184012611-(2-Fluoro-3-hexyloxyphenyl)ethyneYield 63.1%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Procedure

117 g of potassium carbonate and 55.6 g of bromohexane are added to a solution of 53.6 g of 3-bromo-2-fluorophenol in 650 ml of acetone, and the mixture is refluxed for 8 hours. The mixture is filtered, evaporated to ⅓ of the original volume and poured into 600 ml of water. The pH is adjusted to 1 using hydrochloric acid, and the mixture is extracted three times with 150 ml of tert-butyl methyl ether each time. The combined organic phases are concentrated under reduced pressure, and the residue is subjected to vacuum distillation (103° C.; 1 mbar), giving 67 g of 6-bromo-2-hexyloxyfluorobenzene as a colorless oil. 1H-NMR (CDCl3): 6.9-7.1 (m; 3H); 4.0 (t; 2H), 0.9-1.8 (m, 11H), 19F-NMR (CDCl3): −128 ppm. A solution of 67.3 g of 6-bromo-2-hexyloxyfluorobenzene, 24.7 g of 2-methyl-3-butyn-2-ol [115-19-5], 0.7 g of bis(triphenylphosphine)palladium(II) chloride and 0.7 g of copper iodide in 340 ml of triethylamine is refluxed for 5 hours. The mixture is then poured into 1.5 of ice-water, the pH is adjusted to 1 using hydrochloric acid, and the mixture is extracted three-times with 200 ml of tert-butyl methyl ether each time. The combined organic phases are dried under reduced pressure. The crude 4-(2-fluoro-3-hexyloxyphenyl)2methyl-3-butyn-1-ol is refluxed for 3 hours in 1000 ml of toluene together with three mole-equivalents of sodium hydroxide. The mixture is filtered and washed with dilute hydrochloric acid, the solvent is removed by distillation, and the residue is distilled (90° C.; 0.5 mbar), giving 34 g of 1-(2-fluoro-3-hexyloxyphenyl)ethyne.

Workup

  1. extractionthe mixture is extracted three-times with 200 ml of tert-butyl methyl ether each time
  2. customThe combined organic phases are dried under reduced pressure
  3. temperatureThe crude 4-(2-fluoro-3-hexyloxyphenyl)2methyl-3-butyn-1-ol is refluxed for 3 hours in 1000 ml of toluene together with three mole-equivalents of sodium hydroxide
  4. filtrationThe mixture is filtered
  5. washwashed with dilute hydrochloric acid
  6. customthe solvent is removed by distillation
  7. distillationthe residue is distilled (90° C.; 0.5 mbar)

Sources & evidence

ORD record
ord-a95afeb9612645b2b2c5abb1421d9472
Source dataset
uspto-grants-2002_11
Patent number
US06482478B1

Reaction notes

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