Toluene → 1-[2-(4-Fluorophenyl)ethyl]cyclohexan-1-amine

HRID 229412Notes

Reaction equation

HRID 229412 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][CH:3]=1.[C:9]([C:11]1([NH2:17])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)#[CH:10].C(NC(C)C)(C)C.C1(C)C=CC=CC=1>C1COCC1.[Pt]=O.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:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:10][CH2:9][C:11]2([NH2:17])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 1140TolueneHCID 7912DiisopropylamineHCID 96054-FluoroiodobenzeneHCID 1216911-Ethynylcyclohexylamine

Product 1

HCID 671751661-[2-(4-Fluorophenyl)ethyl]cyclohexan-1-amine

Reagents, catalysts & solvents 4

HCID 82844Platinum oxide (PtO)CatalystHCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

2.5 g (11.3 mmol) 1-fluoro-4-iodo-benzene, 1.5 g (11.9 mmol) 1-ethynyl-cyclohexylamine, 793 mg (1.13 mmol) PdCl2(PPh3)2, 67 mg (0.35 mmol) copper iodide and 50 mL diisopropylamine are stirred for 2 hours at 70° C. Then the base is distilled off and the residue is combined with ethyl acetate. The insoluble constituents are filtered off and the filtrate is evaporated down. The alkyne thus prepared is dissolved in 35 mL THF and 35 mL toluene and hydrogenated with platinum oxide as catalyst at normal pressure. The catalyst is separated off and the filtrate is freed from the solvent. The crude product is dissolved in ethyl acetate and combined with 10% hydrochloric acid in ethyl acetate. The precipitated solid is filtered off and washed with ethyl acetate. Yield: 1.3 g (45%; hydrochloride); mass spectroscopy: [M+H]+=222.

Workup

  1. distillationThen the base is distilled off
  2. filtrationThe insoluble constituents are filtered off
  3. customthe filtrate is evaporated down
  4. customThe alkyne thus prepared
  5. customThe catalyst is separated off
  6. dissolutionThe crude product is dissolved in ethyl acetate
  7. filtrationThe precipitated solid is filtered off
  8. washwashed with ethyl acetate

Sources & evidence

ORD record
ord-f636fad3df83406083af2ce852446265
Source dataset
uspto-grants-2009_07
Patent number
US07563806B2

Reaction notes

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