15-Crown-5 → Pitolisant

HRID 222215

Reaktionsgleichung

Reaktionsgleichung von HRID 222215
[N:1]1([CH2:7][CH2:8][CH2:9][O-:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Na+].S(O[CH2:17][CH2:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=1)(=O)(=O)C.C1OCCOCCOCCOCCOC1>C1(C)C=CC=CC=1>[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([CH2:19][CH2:18][CH2:17][O:10][CH2:9][CH2:8][CH2:7][N:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)=[CH:21][CH:22]=1

Komponenten

5

Edukt 3

HCID 3633615-Crown-5HCID 130797053-(4-Chlorophenyl)propyl methanesulfonateHCID 23694275HCID 23694275, Verbindung

Produkt 1

HCID 9948102PitolisantAusbeute 75 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Versuchsvorschrift

According to the method disclosed in EP-982300, Example 78, sodium 3-piperidinopropanolate (2.127 kg; 12.88 mol), 3-(4-chlorophenyl)propyl mesylate (1.121 kg; 4.51 mol) and 0.322 mol of 15-crown-5 in 4.5 kg of dry toluene were refluxed for 4 hours. The solvent was evaporated and the residue purified by column chromatography on silica gel (eluent: methylene chloride/methanol (90/10)). The obtained oil was distilled in a fractionating equipment at reduced pressure (0.3-0.7 mmHg) and with a heating jacket at 207-210° C. The head fractions and the distilled fraction at 0.001-0.010 mmHg with a jacket temperature of 180-200° C. were collected. The obtained oil (1.0 kg; 3.38 mol) corresponds to 1-[3-[3-(4-chlorophenyl)propoxy]propyl]-piperidine. Yield 75%.

Aufarbeitung

  1. temperaturewere refluxed for 4 hours
  2. customThe solvent was evaporated
  3. customthe residue purified by column chromatography on silica gel (eluent: methylene chloride/methanol (90/10))
  4. distillationThe obtained oil was distilled in a fractionating equipment at reduced pressure (0.3-0.7 mmHg) and with a heating jacket at 207-210° C
  5. distillationThe head fractions and the distilled fraction at 0.001-0.010 mmHg with a jacket temperature of 180-200° C. were collected

Quellen und Nachweise

ORD-Eintrag
ord-270153ce4e4349bf8125c262b52132b9
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08207197B2

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