Hydrochloric Acid → 7a-(5,6-Dichloro-3-pyridinyl)-hexahydro-1h-pyrrolizine

HRID 3290

Reaction equation

HRID 3290 reaction equation
[Li]C(C)(C)C.[Cl:6][C:7]1[C:12]([Cl:13])=[CH:11][C:10](I)=[CH:9][N:8]=1.Cl([O-])(=O)(=O)=O.[CH2:20]1[C:27]2[CH2:26][CH2:25][CH2:24][N+:23]=2[CH2:22][CH2:21]1.Cl>CCCCC.CCOCC>[Cl:13][C:12]1[CH:11]=[C:10]([C:27]23[CH2:26][CH2:25][CH2:24][N:23]2[CH2:22][CH2:21][CH2:20]3)[CH:9]=[N:8][C:7]=1[Cl:6]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10878400Pyrrolizinium, 1,2,3,5,6,7-hexahydro-, perchlorateHCID 218928742,3-Dichloro-5-iodopyridineHCID 178418306HCID 178418306, compound

Product 1

HCID 189347577a-(5,6-Dichloro-3-pyridinyl)-hexahydro-1h-pyrrolizineYield 54.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8003PentaneSolvent

Conditions

Temperature
-20 °C

Procedure

A solution of 1.7M tBuLi (4.7 mL, 8.0 mmol) in pentane was added to 2,3-dichloro-5-iodopyridine (from step 8a, 1.0 g, 3.65 mmol) in Et2O (15 mL) precooled to -100° C. After stirring for 2 minutes, 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (1.5 g, 7.3 mmol) was added, and the reaction mixture was allowed to stir for 20 minutes at -100° C. then gradually warm to -20° C. A solution of 2N HCl was added, and the cold bath was removed. After warming to ambient temperature, the reaction mixture was poured over EtOAc and the phases were separated. The aqueous phase was basified with 15% NaOH solution and extracted with CH2Cl2 (2×). The CH2Cl2 phases were combined, dried (MgSO4), concentrated and the residue was chromatographed (silica gel; CHCl3 /MeOH, 99.5:0.5) to afford a light yellow oil (510 mg, 54%). MS (CI/NH3) m/e: 257 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.59-1.71 (m, 2H), 1.80-2.08 (m, 6H), 2.64-2.72 (m, 2H), 3.11-3.20 (m, 2H), 7.99 (d, J=2.2 Hz, 1H), 8.36 (d, J=2.2 Hz, 1H).

Workup

  1. customprecooled to -100° C
  2. stirringto stir for 20 minutes at -100° C.
  3. customthe cold bath was removed
  4. temperatureAfter warming to ambient temperature
  5. additionthe reaction mixture was poured over EtOAc
  6. customthe phases were separated
  7. extractionextracted with CH2Cl2 (2×)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customthe residue was chromatographed (silica gel; CHCl3 /MeOH, 99.5:0.5)

Sources & evidence

ORD record
ord-5e0688aadb234b04b09dab3cc2fb6604
Source dataset
uspto-grants-1998_03
Patent number
US05733912

Linked notes

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