Sodium Hydroxide → Ethyl 4-chloro-7-methoxyquinoline-3-carboxylate

HRID 1865422Notes

Reaction equation

HRID 1865422 reaction equation
O[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:12][CH3:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[C:14]([O:16][CH2:17][CH3:18])=[O:15].[OH-].[Na+].O=P(Cl)(Cl)[Cl:23]>>[Cl:23][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:12][CH3:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[C:14]([O:16][CH2:17][CH3:18])=[O:15]

Participants

4

Reactant 3

HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 178469633HCID 178469633, compound

Product 1

HCID 728976Ethyl 4-chloro-7-methoxyquinoline-3-carboxylate

Procedure

The intermediate from step A (890 mg, mmol) was suspended in POCl3 (5 mL) and refluxed for 1 hour. The reaction was cooled to room temperature and poured into an erlenmeyer flask containing ice and 5 N NaOH (30 mL). The resulting mixture was extracted with ethyl acetate (3×). The organic layer was washed with saturated NaHCO3, saturated NaCl solution dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography using 30% ethyl acetate-hexanes to afford the product as a white solid. 1H NMR (500 MHz, CDCl3): 9.19 (s, 1H), 8.33 (s, J=9.2 Hz, 1H), 7.46 (d, J=2.5 Hz, 1H), 7.36 (dd, J=2.5, 9.1 Hz, 1H), 4.53 (q, J=7.1 Hz, 2H), 4.01 (s, 3H), 1.5 (t, J=7.4 Hz, 3H). LC-MS: 3.22 min; (M+H)=266.1.

Workup

  1. temperaturerefluxed for 1 hour
  2. additionpoured into an erlenmeyer flask
  3. extractionThe resulting mixture was extracted with ethyl acetate (3×)
  4. washThe organic layer was washed with saturated NaHCO3, saturated NaCl solution
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-ade6072014ee42698a8c12150fd16172
Source dataset
uspto-grants-2009_12
Patent number
US07625938B2

Reaction notes

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