Hydrochloric Acid → Flupropadine hydrochloride

HRID 67925

Reaktionsgleichung

Reaktionsgleichung von HRID 67925
[C:1]([CH:5]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]#[CH:13])[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].C(NCC)C.[F:19][C:20]([F:33])([F:32])[C:21]1[CH:22]=[C:23](Br)[CH:24]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:26]=1.[ClH:34]>C(OCC)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.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[ClH:34].[F:19][C:20]([F:32])([F:33])[C:21]1[CH:22]=[C:23]([C:13]#[C:12][CH2:11][N:8]2[CH2:9][CH2:10][CH:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:6][CH2:7]2)[CH:24]=[C:25]([C:27]([F:28])([F:29])[F:30])[CH:26]=1

Komponenten

9

Edukt 4

HCID 313Hydrochloric AcidHCID 8021DiethylamineHCID 676021-Bromo-3,5-bis(trifluoromethyl)benzeneHCID 127998624-Tert-butyl-1-(prop-2-ynyl)piperidine

Produkt 1

HCID 198597Flupropadine hydrochloride

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 11776TriphenylphosphineKatalysatorHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418476HCID 178418476, VerbindungKatalysatorHCID 3283Diethyl EtherLösungsmittel2×

Versuchsvorschrift

4-tert-Butyl-1-(prop-2-ynyl)piperidine (prepared as described in Example 3; 37.3 g) and anhydrous diethylamine (800 ml) were added to 3,5-bistrifluoromethylbromobenzene [which may be prepared as described by E. T. McBee et al, J. Amer. Chem. Soc. (1950), 72, 1651; 61.0 g] and dichlorobis(triphenylphosphine)palladium (0.26 g), copper (I) iodide (0.26 g) and triphenylphosphine (0.26 g) were added with stirring, under an inert atmosphere, to the solution thus obtained. The reaction mixture was heated under reflux for 17 hours and then cooled and filtered. The filtrate was evaporated under reduced pressure (water-pump) and the residual oil thus obtained was dissolved in diethyl ether. A slight excess of a saturated solution of hydrogen chloride in anhydrous diethyl ether was then added, with stirring, to the ethereal solution. The resulting suspension was filtered and the solid residue was washed with diethyl ether and dried under vacuum, to give solid 1-(3,5-bistrifluoromethylphenyl)-3-(4-tert-butylpiperidino)prop-1-yne hydrochloride (72 g), which was then partitioned between a small excess of 2 N aqueous sodium hydroxide solution and diethyl ether. The ethereal layer was dried over anhydrous sodium sulphate and evaporated, to give 1-(3,5-bistrifluoromethylphenyl)-3-(4-tert-butylpiperidino)prop-1-yne in the form of an oil, which had the elementary analysis C: 61.7%; H: 5.8%; N: 3.5% (C20H23F6N requires C: 61.4%; H: 5.9%; N: 3.6%).

Aufarbeitung

  1. additionwere added
  2. customthus obtained
  3. temperatureThe reaction mixture was heated
  4. temperatureunder reflux for 17 hours
  5. temperaturecooled
  6. filtrationfiltered
  7. customThe filtrate was evaporated under reduced pressure (water-pump)
  8. customthe residual oil thus obtained
  9. stirringwith stirring, to the ethereal solution
  10. filtrationThe resulting suspension was filtered
  11. washthe solid residue was washed with diethyl ether
  12. customdried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-931384c64b254b028e517a4149828ca7
Quelldatensatz
uspto-grants-1982_08
Patentnummer
US04347252

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