Formic Acid → 3-[2-Cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]prop-2-enal

HRID 987184Notes

Reaction equation

HRID 987184 reaction equation
[CH:1]1([C:4]2[C:13]([CH:14]=[CH:15][C:16]#N)=[C:12]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)[CH2:3][CH2:2]1.C(O)=[O:26].Cl>[Ni].O>[CH:1]1([C:4]2[C:13]([CH:14]=[CH:15][CH:16]=[O:26])=[C:12]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=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 3

HCID 284Formic AcidHCID 313Hydrochloric AcidHCID 533950303-[2-Cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]prop-2-enenitrile

Product 1

HCID 533949273-[2-Cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]prop-2-enalYield 96.7%

Reagents, catalysts & solvents 2

HCID 935NickelCatalyst2×HCID 962WaterSolvent3×

Procedure

In a 5 mL-volume glass flask equipped with a stirrer, a thermometer and a dropping funnel were placed under nitrogen atmosphere 314 mg (1.0 mmol) of 3-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]prop-2-enenitrile (prepared in Reference Example 1), 2.25 mL of formic acid (60 mmol, mol calculated as 100% formic acid), 0.75 mL of water, and 620 mg (5.3 mmol as nickel atom) of water-containing developed Raney-nickel (NDHT-90, nickel content 50 wt. %, available from Kawaken Fine Chemical Co., Ltd.). The content was reacted at 80° C. for hours. After the reaction was complete, the content was cooled to room temperature. After addition of 9 mL of water and 9 mL of hydrochloric acid (1 mol/L), the catalyst was removed by filtration using a celite. The celite was washed with two portions of 2-butanol (1 mL) and two portions of toluene (9 mL). The organic portion was dried over anhydrous magnesium sulfate. The dried organic portion was filtered and the filtrate was concentrated under reduced pressure to give 307 mg (yield 91%) of 3-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]prop-2-enal as yellow solid (purity 97%, in terms of an area percent according to high performance liquid chromatography).

Workup

  1. customIn a 5 mL-volume glass flask equipped with a stirrer
  2. customThe content was reacted at 80° C. for hours
  3. customthe catalyst was removed by filtration
  4. washThe celite was washed with two portions of 2-butanol (1 mL) and two portions of toluene (9 mL)
  5. dry with materialThe organic portion was dried over anhydrous magnesium sulfate
  6. filtrationThe dried organic portion was filtered
  7. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-82bbf682449a4f588ecd23d03e5830f7
Source dataset
uspto-grants-2003_10
Patent number
US06630591B2

Reaction notes

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