Hydrochloric Acid → 7-Chloro-6-methoxy-2-methylquinoline

HRID 931698Notes

Reaction equation

HRID 931698 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][CH3:10])[NH2:5].Cl.[CH:12](=O)/[CH:13]=[CH:14]/[CH3:15]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:6]([CH:12]=[CH:13][C:14]([CH3:15])=[N:5]2)=[CH:7][C:8]=1[O:9][CH3:10]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 214413-Chloro-4-methoxyanilineHCID 447466Crotonaldehyde

Product 1

HCID 666317827-Chloro-6-methoxy-2-methylquinolineYield 50.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To 3-chloro-4-methoxyaniline (1A) (5.0 g, 31.7 mmol) was added 6 M HCl (100 mL) and the reaction was heated to 100° C. with stirring. Toluene (30 mL) was added followed by the slow addition of crotonaldehyde (5.3 mL, 63.5 mmol) at 100° C. The mixture was stirred at 100° C. for 2 hours and cooled to room temperature. The water layer was separated and neutralized with 2 M NaOH solution to pH ˜8. The solid that formed was filtered and collected. The crude product was purified by flash column chromatography to give 1B as white solid (3.3 g, 50%). LCMS-ESI+ (m/z): 208.2, 210.2 (M+H)+.

Workup

  1. stirringThe mixture was stirred at 100° C. for 2 hours
  2. temperaturecooled to room temperature
  3. customThe water layer was separated
  4. customThe solid that formed
  5. filtrationwas filtered
  6. customcollected
  7. customThe crude product was purified by flash column chromatography

Sources & evidence

ORD record
ord-3bf2392187b541a4a7bf5ce8cbc548cc
Source dataset
uspto-grants-2016_03
Patent number
US09296758B2

Reaction notes

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