Hydrochloric Acid → Benzyl 6,7-dimethoxy-2-methyl-4-oxo-1,2,3,4-tetrahydroquinoline-1-carboxylate

HRID 370031Notes

Reaction equation

HRID 370031 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.[CH3:17][Mg]Cl.Cl[C:21]([O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:22].Cl>O1CCCC1>[CH2:24]([O:23][C:21]([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[CH3:17])=[O:22])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 10387Benzyl chloroformateHCID 154806724,6,7-TrimethoxyquinolineHCID 178418332HCID 178418332, compound

Product 1

HCID 15480673Benzyl 6,7-dimethoxy-2-methyl-4-oxo-1,2,3,4-tetrahydroquinoline-1-carboxylateYield 57%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

4,6,7-Trimethoxyquinoline (1.0 g, 4.6 mmol) was dissolved in anhydrous tetrahydrofuran (15 mL). The mixture was cooled to -78° C., and methyl magnesium chloride (2.3 mL of a 3.0M solution in tetrahydrofuran, 6.9 mmol) was added. The mixture was stirred at -78° C. for 1 h, then benzyl chloroformate (1.0 mL, 6.9 mmol) was added. The reaction was warmed to room temperature over 30 min, then 8 mL of a 1N aqueous HCl solution was added. After 30 minutes, the tetrahydrofuran was removed in vacuo, and the remaining aqueous phase was extracted with ethyl acetate (3×30 mL). The organic phases were combined and washed with water (15 mL), dried over sodium sulfate, filtered, and concentrated in vacuo to give 1.5 g of crude product. Purification by silica gel chromatography using 0-50% ethyl acetate/hexanes as eluent afforded 0.91 g of the desired product (57%). 1H NMR (CDCl3) δ 1.25 (d, 3H), 2.5 (d, 1H), 3.0 (dd, 1H), 3.7 (s, 3H), 3.9 (s, 3H), 5.1-5.3 (m, 5.2 (d, 1H), 5.4 (d, 1H), 7.3-7.5 (m, 7H).

Workup

  1. temperatureThe reaction was warmed to room temperature over 30 min
  2. waitAfter 30 minutes
  3. customthe tetrahydrofuran was removed in vacuo
  4. extractionthe remaining aqueous phase was extracted with ethyl acetate (3×30 mL)
  5. washwashed with water (15 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give 1.5 g of crude product
  10. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-2f9d5f068b6c4935a19f9c18af946ba4
Source dataset
uspto-grants-2000_10
Patent number
US06140342

Reaction notes

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