Hydrochloric Acid → 3-[2-Cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]prop-2-enenitrile

HRID 1264174Notes

Reaction equation

HRID 1264174 reaction equation
[CH:1]1([C:4]2[C:13]([CH:14]=O)=[C:12]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)[CH2:3][CH2:2]1.[C:23](#[N:25])[CH3:24].C[O-].[Na+].Cl>C1(C)C=CC=CC=1>[CH:1]1([C:4]2[C:13]([CH:14]=[CH:24][C:23]#[N:25])=[C:12]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 99479742-Cyclopropyl-4-(4-fluorophenyl)-3-quinolinecarboxaldehydeHCID 10942334Sodium Methoxide

Product 1

HCID 533950303-[2-Cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]prop-2-enenitrileYield 96%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

In a 200 mL-volume glass flask equipped with a stirrer and a thermometer were placed under argon atmosphere 9.2 g (31.6 mmol) of 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carbaldehyde, 7.5 mL (143 mmol) of acetonitrile, 45 mL of toluene (dielectric constant at 25° C.: 2.38), and 1.99 g (36.8 mmol) of sodium methoxide. The content was reacted at 50° C. for 8 hours. The resulting mixture was chilled in an ice bath. To the chilled mixture were slowly added under stirring 40 mL of toluene and 34.0 mL (34.0 mmol) of hydrochloric acid (1 mol/L), successively. The separated organic portion was taken out. After washing with 30 mL of saturated aqueous sodium chloride solution, the organic portion was dried over anhydrous magnesium sulfate. The organic portion was then filtered and analyzed by high performance liquid chromatography (absolute quantitative analysis). It was confirmed that 9.52 g (yield: 96%) of 3-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]prop-2-enenitrile was produced. The organic portion was concentrated under reduced pressure, and the residue was crystallized from ethyl acetate/hexane (15/85, vol. ratio) to obtain 9.29 g (yield 88%) of 3-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]prop-2-enenitrile as a yellow crystalline product (purity: 94%, measured by high performance liquid chromatography).

Workup

  1. customIn a 200 mL-volume glass flask equipped with a stirrer
  2. customThe content was reacted at 50° C. for 8 hours
  3. temperatureThe resulting mixture was chilled in an ice bath
  4. additionTo the chilled mixture were slowly added
  5. washAfter washing with 30 mL of saturated aqueous sodium chloride solution
  6. dry with materialthe organic portion was dried over anhydrous magnesium sulfate
  7. filtrationThe organic portion was then filtered

Sources & evidence

ORD record
ord-a9a41d9a2f8b4a5782b87d9a2e8030c1
Source dataset
uspto-grants-2003_04
Patent number
US06541636B2

Reaction notes

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