Chloroform → Ethyl 4,5,7-trichloro-8-methoxyquinoline-3-carboxylate

HRID 1754101Notes

Reaction equation

HRID 1754101 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[Cl:16])=[CH:13][CH:12]=C[C:10]=2[O:17][CH3:18])=[O:5])[CH3:2].S(Cl)([Cl:22])(=O)=O.[CH:24]([Cl:27])(Cl)Cl>>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[Cl:16])=[C:13]([Cl:22])[CH:12]=[C:24]([Cl:27])[C:10]=2[O:17][CH3:18])=[O:5])[CH3:2]

Participants

4

Reactant 3

HCID 6212Chloroform2×HCID 24648Sulfuryl chloride2×HCID 3045573-Quinolinecarboxylic acid, 4-chloro-8-methoxy-, ethyl ester

Product 1

HCID 57939336Ethyl 4,5,7-trichloro-8-methoxyquinoline-3-carboxylateYield 29%

Conditions

Temperature
65 °C

Procedure

To a stirred solution of 4-chloro-8-methoxy-quinoline-3-carboxylic acid ethyl ester (1.00 g, 3.76 mmol) in chloroform (50 mL) was added, dropwise over 1 h, a solution of sulfuryl chloride (15 mL) in chloroform (15 mL) whilst maintaining the temperature at 25-30° C. The solution was then heated at 60-70° C. for 48 h. During this time, further sulfuryl chloride (2 mL) was added at regular intervals (2, 24 and 30 h). The solution was allowed to cool to RT and added to ice-aqueous ammonia, adjusting the pH to 8. The mixture was then extracted with dichloromethane (20 mL×3), the extracts combined and concentrated. Column chromatography (silica gel, dichloromethane/methanol (100:1)) gave the title compound 26 as a cream solid (0.36 g, 29%). 1H-NMR (CDCl3, 400 MHz): δ 9.04 (s, 1 H), 7.78 (s, 1 H), 4.51 (q, J=7.1, 2 H), 4.14 (s, 3 H), 1.46 (t, J=7.1, 3 H).

Workup

  1. temperatureto cool to RT
  2. additionadded to ice-aqueous ammonia
  3. extractionThe mixture was then extracted with dichloromethane (20 mL×3)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-e7f4c29a85f047f29e0c5db2dfa4534a
Source dataset
uspto-grants-2015_10
Patent number
US09169211B2

Reaction notes

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