Phosphoric Acid → 8-Bromo-5-fluoro-2-propylquinoline

HRID 1095229Notes

Reaction equation

HRID 1095229 reaction equation
[Br:1][C:2]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][C:3]=1[NH2:4].[N+]([C:13]1[CH:14]=[C:15](S(O)(=O)=O)[CH:16]=[CH:17][CH:18]=1)([O-])=O.P(=O)(O)(O)O.C(=O)/C=C/CCC.O.N>O>[Br:1][C:2]1[CH:8]=[CH:7][C:6]([F:9])=[C:5]2[C:3]=1[N:4]=[C:18]([CH2:17][CH2:16][CH3:15])[CH:13]=[CH:14]2

Participants

7

Reactant 5

HCID 1004Phosphoric AcidHCID 73873-Nitrobenzenesulfonic acidHCID 27733172-Bromo-5-fluoroanilineHCID 5281168trans-2-HexenalHCID 12896473Azane;hydrate

Product 1

HCID 667841288-Bromo-5-fluoro-2-propylquinolineYield 17.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

2-Bromo-5-fluoro-aniline (5.00 g, 95 mass % article, 25.0 mmol), m-nitrobenzenesulfonic acid (2.65 g, 13.0 mmol), 20.0 mL of 85 wt % aqueous phosphoric acid solution and ferrous sulfate heptahydrate (65.5 mg, 0.250 mmol) were placed in a 100 mL three-neck flask equipped with a magnetic stirrer, a reflux condenser, a thermometer and a dropping funnel and the mixture was heated to 80° C. in an oil bath. Subsequently, trans-2-hexenal (6.51 g, 98 mass % article, 65.0 mmol) was added dropwise thereto through the dropping funnel for 1 hour. After completion of the dropwise addition, the mixture was heated and stirred at 100° C. for 2 hours. Then, the reaction mixture was poured into water and neutralized to pH 7 by ammonia water. The neutralized liquid was extracted with dichloromethane, and then dichloromethane was removed under reduced pressure. The resulting crude reaction product was purified by column chromatography (Hexane/AcOEt=100/0→1/10) using silica gel, followed by drying under reduced pressure to give 625 mg of 8-bromo-5-fluoro-2-propylquinoline as a yellowish white solid (yield: 9.33%).

Workup

  1. customequipped with a magnetic stirrer, a reflux condenser
  2. additionAfter completion of the dropwise addition
  3. temperaturethe mixture was heated
  4. extractionThe neutralized liquid was extracted with dichloromethane
  5. customdichloromethane was removed under reduced pressure
  6. customThe resulting crude reaction product
  7. customwas purified by column chromatography (Hexane/AcOEt=100/0→1/10)
  8. customby drying under reduced pressure

Sources & evidence

ORD record
ord-0c3242fa9e9d4254a1a831b652d526be
Source dataset
uspto-grants-2012_03
Patent number
US08137821B2

Reaction notes

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