Hydrochloric Acid → 7a-(2,6-dichloro-3-pyridinyl)-hexahydro-1H-pyrrolizine

HRID 3295

Reaktionsgleichung

Reaktionsgleichung von HRID 3295
[Li]CCCC.C(NC(C)C)(C)C.[Cl:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[N:15]=1.Cl([O-])(=O)(=O)=O.[CH2:26]1[C:33]2[CH2:32][CH2:31][CH2:30][N+:29]=2[CH2:28][CH2:27]1.Cl>C1COCC1.CCOC(C)=O>[Cl:13][C:14]1[C:19]([C:33]23[CH2:32][CH2:31][CH2:30][N:29]2[CH2:28][CH2:27][CH2:26]3)=[CH:18][CH:17]=[C:16]([Cl:20])[N:15]=1

Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 169892,6-DichloropyridineHCID 10878400Pyrrolizinium, 1,2,3,5,6,7-hexahydro-, perchlorateHCID 178418339Butyllithium

Produkt 1

HCID 189347197a-(2,6-dichloro-3-pyridinyl)-hexahydro-1H-pyrrolizineAusbeute 17,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

A solution of 2.5M nBuLi (675 μL, 1.7 mmol) in hexanes was added to diisopropylamine (220 μL, 1.7 mmol) in THF (4.5 mL) at ambient temperature. After 10 minutes of stirring, the reaction mixture was cooled to -78° C., 2,6-dichloropyridine (237 μL, 1.60 mmol) was added neat, and stirring was continued for 1 hour at -78° C. 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (500 mg, 2.40 mmol) was added, and the reaction mixture was allowed to stir for 2 hours at -78° C. then warm to ambient temperature. A solution of 2N HCl was added, and the mixture was then poured over EtOAc. The phases were separated, and the aqueous phase was basified with 15% NaOH and extracted with CH2Cl2 (2×). The CH2Cl2 fractions were combined, dried (MgSO4) and concentrated, and the residue was chromatographed (silica gel; CHCl3 /MeOH, 98:2) to afford a clear oil (70.6 mg, 17%). MS (CI/NH3) m/e: 257/259 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.47-1.61 (m, 2H), 1.77-1.90 (m, 2H), 2.10-2.25 (m, 4H), 2.67-2.75 (m, 2H), 3.03-3.11 (m, 2H), 7.19 (d, J=8.5 Hz, 1H), 8.37 (d, J=8.5 Hz, 1H).

Aufarbeitung

  1. stirringstirring
  2. waitwas continued for 1 hour at -78° C
  3. stirringto stir for 2 hours at -78° C.
  4. temperaturethen warm to ambient temperature
  5. customThe phases were separated
  6. extractionextracted with CH2Cl2 (2×)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customthe residue was chromatographed (silica gel; CHCl3 /MeOH, 98:2)

Quellen und Nachweise

ORD-Eintrag
ord-c171067de28743cf9e9bdee6ad6c9574
Quelldatensatz
uspto-grants-1998_03
Patentnummer
US05733912

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