Hydrochloric Acid → Flupropadine hydrochloride

HRID 67925

반응식

HRID 67925 반응식
[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

참가 물질

9

반응물 4

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

생성물 1

HCID 198597Flupropadine hydrochloride

시약·촉매·용매 4

HCID 11776Triphenylphosphine촉매HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418476HCID 178418476, 화합물촉매HCID 3283Diethyl Ether용매2회

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-931384c64b254b028e517a4149828ca7
출처 데이터셋
uspto-grants-1982_08
특허 번호
US04347252

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