7a-(6-Chloro-5-methyl-3-pyridinyl)-hexahydro-1H-pyrrolizine → HCID 18934718, compound

HRID 3323Notes

Reaction equation

HRID 3323 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]23[CH2:15][CH2:14][CH2:13][N:12]2[CH2:11][CH2:10][CH2:9]3)=[CH:4][C:3]=1[CH3:16].[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH3:16][C:3]1[CH:4]=[C:5]([C:8]23[CH2:15][CH2:14][CH2:13][N:12]2[CH2:11][CH2:10][CH2:9]3)[CH:6]=[N:7][CH:2]=1

Participants

4

Reactant 2

HCID 97947077a-(6-Chloro-5-methyl-3-pyridinyl)-hexahydro-1H-pyrrolizineHCID 21226445Aluminium lithium hydride3×

Product 1

HCID 18934718HCID 18934718, compoundYield 49.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

7a-(6-Chloro-5-methyl-3-pyridinyl)-hexahydro-1H-pyrrolizine (274 mg, 1.16 mmol, from Example 19c) and LAH (1.0M in THF, 1.2 mL, 1.16 mmol) were added to THF (4.5 mL), and the mixture was stirred at room temperature for 4 hours. An additional amount of LAH (1.0M in THF, 1.2 mL, 1.16 mmol) was added, and the reaction was stirred overnight. A further amount of LAH (2 equivalents) was added, and the reaction was stirred at room temperature for 24 hours and at 80° C. for 5 hours. The reaction was quenched with 10% K2CO3 solution, and the resulting slurry was filtered. The filtrate was diluted with EtOAc and 15% NaOH, and the phases were separated. The aqueous phase was extracted with methylene chloride, and all the organic solutions were combined, dried and concentrated. The residue was chromatographed (silica gel; CHCl3 /MeOH, 98:2) to afford the title compound as an oil (116 mg, 49%): 1H NMR (CDCl3, 300 MHz) δ1.57-1.71 (m, 2H), 1.77-2.06 (m, 6H), 2.32 (s, 3H), 2.66-2.74 (m, 2H), 3.12-3.19 (m, 2H), 7.63 (s, 1H), 8.24 (s, 1H), 8.50 (s, 1H); MS (CI/NH3) m/z: 203 (M+H)+.

Workup

  1. stirringthe reaction was stirred overnight
  2. stirringthe reaction was stirred at room temperature for 24 hours and at 80° C. for 5 hours
  3. customThe reaction was quenched with 10% K2CO3 solution
  4. filtrationthe resulting slurry was filtered
  5. additionThe filtrate was diluted with EtOAc and 15% NaOH
  6. customthe phases were separated
  7. extractionThe aqueous phase was extracted with methylene chloride
  8. customdried
  9. concentrationconcentrated
  10. customThe residue was chromatographed (silica gel; CHCl3 /MeOH, 98:2)

Sources & evidence

ORD record
ord-e9f462982753453bbfd8fa8e28ec7c0c
Source dataset
uspto-grants-1998_03
Patent number
US05733912

Reaction notes

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