1-Ethynyl-4-propylcyclohexane → 1-Ethoxy-2,3-difluoro-4-(4-propylcyclohexylethynyl)benzene

HRID 1841829Notes

Reaction equation

HRID 1841829 reaction equation
[C:1]([CH:3]1[CH2:8][CH2:7][CH:6]([CH2:9][CH2:10][CH3:11])[CH2:5][CH2:4]1)#[CH:2].Br[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH3:21])=[C:15]([F:22])[C:14]=1[F:23]>C(N(CC)CC)C.CC(OC)(C)C.Cl.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>[CH2:20]([O:19][C:16]1[CH:17]=[CH:18][C:13]([C:2]#[C:1][CH:3]2[CH2:8][CH2:7][CH:6]([CH2:9][CH2:10][CH3:11])[CH2:5][CH2:4]2)=[C:14]([F:23])[C:15]=1[F:22])[CH3:21]

Participants

8

Reactant 2

HCID 218706261-Ethynyl-4-propylcyclohexaneHCID 269854911-Bromo-4-ethoxy-2,3-difluorobenzene

Product 1

HCID 199845241-Ethoxy-2,3-difluoro-4-(4-propylcyclohexylethynyl)benzene

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 313Hydrochloric AcidSolventHCID 8471TriethylamineSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 20.6 g (0.14 mol) of 1-ethynyl-4-propylcyclohexane, 25.0 g (0.11 mol) of 1-bromo-4-ethoxy-2,3-difluorobenzene, 2.22 g (3.16 mmol) of bis(triphenylphosphine)palladium(II) chloride and 603 mg (3.16 mmol) of copper(I) iodide in 440 ml of triethylamine is warmed at 50° C. for 19 h. After cooling, the mixture is diluted with MTBE and neutralised using dil. hydrochloric acid. The organic phase is separated off, and the aqueous phase is extracted with MTBE. The combined organic phases are washed with sodium chloride solution and dried using sodium sulfate. The solution is concentrated to dryness, and the residue is purified by column chromatography (SiO2, n-heptane:chlorobutane=9:1). The further purification is carried out by recrystallisation from n-heptane, giving 1-ethoxy-2,3-difluoro-4-(4-propylcyclohexylethynyl)benzene as a colourless solid (m.p. 64° C.). This has the phase sequence: C 64° C. I. The properties, extrapolated from a 10% solution in ZLI-4792, are:

Workup

  1. temperatureAfter cooling
  2. customThe organic phase is separated off
  3. extractionthe aqueous phase is extracted with MTBE
  4. washThe combined organic phases are washed with sodium chloride solution
  5. customdried
  6. concentrationThe solution is concentrated to dryness
  7. customthe residue is purified by column chromatography (SiO2, n-heptane:chlorobutane=9:1)
  8. customThe further purification
  9. customis carried out by recrystallisation from n-heptane

Sources & evidence

ORD record
ord-e76b039464e14f3dad843f034d8cb177
Source dataset
uspto-grants-2015_02
Patent number
US08945420B2

Reaction notes

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