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

HRID 3295

Reaction equation

HRID 3295 reaction equation
[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

Participants

8

Reactant 5

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

Product 1

HCID 189347197a-(2,6-dichloro-3-pyridinyl)-hexahydro-1H-pyrrolizineYield 17.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-c171067de28743cf9e9bdee6ad6c9574
Source dataset
uspto-grants-1998_03
Patent number
US05733912

Linked notes

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