Hydrochloric Acid → 6,7-Dimethoxy-2-isopropyl-4-oxo-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester

HRID 1355646Notes

Reaction equation

HRID 1355646 reaction equation
C[O:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:15][CH3:16])=[C:10]([O:13][CH3:14])[CH:11]=2)[N:6]=[CH:5][CH:4]=1.[CH:17]([Mg]Cl)([CH3:19])[CH3:18].Cl[C:23]([O:25][CH2:26][CH3:27])=[O:24].Cl>O1CCCC1>[CH2:26]([O:25][C:23]([N:6]1[C:7]2[C:12](=[CH:11][C:10]([O:13][CH3:14])=[C:9]([O:15][CH3:16])[CH:8]=2)[C:3](=[O:2])[CH2:4][CH:5]1[CH:17]([CH3:19])[CH3:18])=[O:24])[CH3:27]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 10928Ethyl chloroformateHCID 154806724,6,7-TrimethoxyquinolineHCID 178418918HCID 178418918, compound

Product 1

HCID 696938456,7-Dimethoxy-2-isopropyl-4-oxo-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl esterYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

4,6,7-Trimethoxyquinoline (0.3 g, 1.4 mmol) was dissolved in anhydrous tetrahydrofuran (6 mL). The mixture was cooled to −78° C., and isopropyl magnesium chloride (0.8 mL of a 2M solution in tetrahydrofuran, 1.6 mmol) was added. The mixture was stirred at −78° C. for 10 min, then ethyl chloroformate (0.16 mL, 1.6 mmol) was added. The reaction was warmed to room temperature and stirred overnight, then 1N HCl (6 mL) was added. After stirring for 1 h, the tetrahydrofuran was removed in vacuo, and the remaining aqueous phase was extracted with ethyl acetate (3×50 mL). The organic phases were combined and washed with water (15 mL), dried over sodium sulfate, filtered, and concentrated in vacuo to give 0.26 g crude product. Purification by silica gel chromatography using 0-40% ethyl acetate/hexanes as eluent afforded the title product (0.23 g, 51%). 1H NMR (CDCl3) δ 0.85 (d, 3H), 0.9 (d, 3H), 1.33 (t, 3H), 1.8 (m, 1H), 2.8 (dd, 1H), 2.93 (dd, 1H), 3.9 (s, 3H), 3.95 (s, 3H), 4.3 (m, 2H), 4.5 (m, 1H), 7.3 (bs, 1H), 7.37 (s, 1H).

Workup

  1. temperatureThe reaction was warmed to room temperature
  2. stirringstirred overnight
  3. stirringAfter stirring for 1 h
  4. customthe tetrahydrofuran was removed in vacuo
  5. extractionthe remaining aqueous phase was extracted with ethyl acetate (3×50 mL)
  6. washwashed with water (15 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give 0.26 g crude product
  11. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-0891ac97af704ac3bf920813ed7f0753
Source dataset
uspto-grants-2003_07
Patent number
US06586448B1

Reaction notes

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