Water → 7-Allyl-5-fluoro-8-quinolinol

HRID 1095220Notes

Reaction equation

HRID 1095220 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:13]=[CH:12][C:11]([OH:14])=[C:10]2[C:5]=1[CH:6]=[CH:7][CH:8]=[N:9]2.[CH2:15](Br)[CH:16]=[CH2:17].O>CN(C=O)C>[CH2:17]([C:12]1[C:11]([OH:14])=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[N:9]2)=[C:4]([F:3])[CH:13]=1)[CH:16]=[CH2:15]

Participants

6

Reactant 4

HCID 962WaterHCID 7841Allyl bromideHCID 24758Sodium hydrideHCID 2179075-Fluoro-8-quinolinol

Product 1

HCID 667838147-Allyl-5-fluoro-8-quinolinolYield 96.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

After a 100 mL three-neck flask equipped with a magnetic stirrer, a reflux condenser, a thermometer and a dropping funnel was replaced with Ar, 5 mL of DMF and NaH (0.88 g, 60 mass % article, 22.0 mmol) were placed therein and the temperature of the mixture was cooled to 0° C. or lower in an ice bath, followed by stirring of the mixture. 5-Fluoro-8-quinolinol (3.42 g, 21.0 mmol) dissolved in 30.0 mL of DMF was added dropwise to this over 1 hour. After the mixture was stirred at the same temperature for 30 minutes, allyl bromide (2.54 g, 21.0 mmol) was added dropwise thereto. Further, the mixture was stirred at the same temperature for 30 minutes, and then the internal temperature was slowly raised to 150° C. and the mixture was heated and stirred for 2 hours. This was cooled to room temperature, and then the reaction mixture was poured into water and the mixture was extracted with ethyl acetate. Then, ethyl acetate was removed under reduced pressure and the resulting crude reaction product was purified by column chromatography (Hexane/AcOEt=100/0→1/1) using silica gel, followed by drying under reduced pressure to give 4.10 g of 7-allyl-5-fluoro-8-quinolinol as a white solid (yield: 96.0%).

Workup

  1. customAfter a 100 mL three-neck flask equipped with a magnetic stirrer, a reflux condenser
  2. additionwas added dropwise to this over 1 hour
  3. stirringAfter the mixture was stirred at the same temperature for 30 minutes
  4. stirringFurther, the mixture was stirred at the same temperature for 30 minutes
  5. temperaturethe internal temperature was slowly raised to 150° C.
  6. temperaturethe mixture was heated
  7. stirringstirred for 2 hours
  8. temperatureThis was cooled to room temperature
  9. extractionthe mixture was extracted with ethyl acetate
  10. customThen, ethyl acetate was removed under reduced pressure
  11. customthe resulting crude reaction product
  12. customwas purified by column chromatography (Hexane/AcOEt=100/0→1/1)
  13. customby drying under reduced pressure

Sources & evidence

ORD record
ord-d8f6e2a6d51746cd9c57ec93f914072f
Source dataset
uspto-grants-2012_03
Patent number
US08137821B2

Reaction notes

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