Sodium Hydroxide → 8-Bromoquinoline-4-carbaldehyde

HRID 2207718Notes

Reaction equation

HRID 2207718 reaction equation
[Se](=O)=O.[Br:4][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:14]=1[N:13]=[CH:12][CH:11]=[C:10]2[CH3:15].[OH-:16].[Na+]>O1CCOCC1.O>[Br:4][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:14]=1[N:13]=[CH:12][CH:11]=[C:10]2[CH:15]=[O:16]

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 24007Selenium DioxideHCID 153799098-Bromo-4-methylquinoline2×

Product 1

HCID 468357198-Bromoquinoline-4-carbaldehyde

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
77 °C

Procedure

As shown in step 9-iii of Scheme 9, selenium dioxide (764.7 g, 6.754 mol) was taken up in 3.25 L of dioxane and 500 mL of water. The stirred solution was heated to 77° C. and 8-bromo-4-methylquinoline (compound 2030, 500 g, 2.251 mol) was added in one portion. The reaction mixture was stirred at reflux for 30 minutes and then cooled with a water bath to about 45° C., at which temperature a precipitate was observed. The suspension was filtered through diatomaceous earth which was subsequently washed with the hot THF to dissolve any residual solids. The filtrate was concentrated to a minimum volume under reduced pressure and 2M NaOH (2.81 L, 5.63 mol) was added to achieve a pH of 8 to 9. The reaction mixture was stirred at this pH for 30 minutes. A precipitate resulted which was collected by filtration and air-dried overnight to produce 8-bromoquinoline-4-carbaldehyde (compound 2031) as an yellowish solid: MS=236.16 (M+H); 1H NMR (300 MHz, CDCl3) δ 10.52 (s, 1H), 9.34 (d, J=4.2 Hz, 1H), 9.05 (dd, J=8.5, 1.2 Hz, 1H), 8.18 (dd, J=7.5, 1.3 Hz, 1H), 7.88 (d, J=4.2 Hz, 1H), 7.60 (dd, J=8.5, 7.5 Hz, 1H). This material was used as is in subsequent reactions.

Workup

  1. temperatureat reflux for 30 minutes
  2. temperaturecooled with a water bath to about 45° C., at which temperature a precipitate
  3. filtrationThe suspension was filtered through diatomaceous earth which
  4. washwas subsequently washed with the hot THF
  5. dissolutionto dissolve any residual solids
  6. additionwas added
  7. stirringThe reaction mixture was stirred at this pH for 30 minutes
  8. customA precipitate resulted which
  9. filtrationwas collected by filtration
  10. customair-dried overnight

Sources & evidence

ORD record
ord-5cfe96c5f6404d3eab8b9191bebef534
Source dataset
uspto-grants-2016_06
Patent number
US09376448B2

Reaction notes

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