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

HRID 1264169Notes

Reaction equation

HRID 1264169 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.[H-].[Na+].C(OCC)=O.Cl.[C:31](#[N:33])[CH3:32]>>[CH:1]1([C:4]2[C:13]([CH:14]=[CH:32][C:31]#[N:33])=[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 5

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 8025Ethyl formateHCID 24758Sodium hydrideHCID 99479742-Cyclopropyl-4-(4-fluorophenyl)-3-quinolinecarboxaldehyde

Product 1

HCID 533950303-[2-Cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]prop-2-enenitrileYield 85%

Procedure

In a 100 mL-volume glass flask equipped with a stirrer, a thermometer and a dropping funnel were placed under argon atmosphere 1.94 g (6.66 mmol) of 2-cyclo-propyl-4-(4-fluorophenyl)quinoline-3-carbaldehyde, 10 mL of acetonitrile and 0.422 g (10.6 mmol). of sodium hydride (purity: 60%). The content was stirred at room temperature for 2 hours. The resulting mixture was chilled to −10° C. To the chilled mixture was added 20 mL (248 mmol) of ethyl formate, and the mixture was stirred for 4 hours at the same temperature. Subsequently, to the mixture was slowly added 11 mL of hydrochloric acid (1 mol/L) which was previously chilled in an ice bath. In the mixture, an organic portion separated from an aqueous portion. The organic portion was taken out, washed with two 10 mL portions of saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The organic portion was filtered and analyzed by high performance liquid chromatography (absolute quantitative analysis). It was confirmed that 1.71 g (yield: 85%) of 3-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]prop-2-enenitrile was produced. The organic portion was concentrated under reduced pressure to leave a yellow solid residue. The solid residue was recrystallized from toluene/hexane (1/8, vol. ratio) to obtain 1.79 g of 3-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]prop-2-enenitrile as a yellow crystalline product (purity: 97%). The obtained 3-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]prop-2-enenitrile had the following characteristics:

Workup

  1. customIn a 100 mL-volume glass flask equipped with a stirrer
  2. temperatureThe resulting mixture was chilled to −10° C
  3. stirringthe mixture was stirred for 4 hours at the same temperature
  4. temperaturewas previously chilled in an ice bath
  5. customIn the mixture, an organic portion separated from an aqueous portion
  6. washwashed with two 10 mL portions of saturated aqueous sodium chloride solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationThe organic portion was filtered

Sources & evidence

ORD record
ord-9206bb425ee84ed9a30dfd78ce369353
Source dataset
uspto-grants-2003_04
Patent number
US06541636B2

Reaction notes

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