Hydrochloric Acid → 2-chloro-4-phenyl-6,7-dihydro-5H-cyclopenta[b]pyridine-3-carbonitrile

HRID 1916264Notes

Reaction equation

HRID 1916264 reaction equation
N[C:2]1[N:7]=[C:6]2[CH2:8][CH2:9][CH2:10][C:5]2=[C:4]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:3]=1[C:17]#[N:18].N(OCCC(C)C)=O.[ClH:27]>O1CCCC1.[Cu](Cl)Cl>[Cl:27][C:2]1[N:7]=[C:6]2[CH2:8][CH2:9][CH2:10][C:5]2=[C:4]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:3]=1[C:17]#[N:18]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 8053Isoamyl NitriteHCID 6681092-amino-4-phenyl-6,7-dihydro-5H-cyclopenta[b]pyridine-3-carbonitrile

Product 1

HCID 581581352-chloro-4-phenyl-6,7-dihydro-5H-cyclopenta[b]pyridine-3-carbonitrile

Reagents, catalysts & solvents 2

HCID 24014Cupric ChlorideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Under argon, 500 mg (2.12 mmol) of the compound from Example 16A, 0.57 ml (4.25 mmol) of isopentyl nitrite and 571 mg (4.25 mmol) of copper(II) chloride in 21 ml of tetrahydrofuran were heated under reflux for 6 h. After cooling, 1 N hydrochloric acid was added and the reaction mixture was extracted with ethyl acetate. The organic phase was washed with water and a saturated aqueous sodium chloride solution, dried over magnesium sulfate and freed from the solvent on a rotary evaporator. The residue was purified by preparative HPLC (column: YMC GEL ODS-AQ S-5, 15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5).

Workup

  1. temperatureunder reflux for 6 h
  2. temperatureAfter cooling
  3. extractionthe reaction mixture was extracted with ethyl acetate
  4. washThe organic phase was washed with water
  5. dry with materiala saturated aqueous sodium chloride solution, dried over magnesium sulfate
  6. customfreed from the solvent on a rotary evaporator
  7. customThe residue was purified by preparative HPLC (column: YMC GEL ODS-AQ S-5, 15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5)

Sources & evidence

ORD record
ord-effb52970d234eeca8bac2eadb0e49d8
Source dataset
uspto-grants-2013_12
Patent number
US08618119B2

Reaction notes

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