Hydrochloric Acid → HCID 178487676, compound

HRID 1815692Notes

Reaction equation

HRID 1815692 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([NH2:9])[CH:4]=1.[C:10]([CH2:18][C:19](OCC)=[O:20])(=O)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.Cl>C1(C)C=CC=CC=1>[OH:20][C:19]1[C:6]2[C:5](=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)[N:9]=[C:10]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:18]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 7170Ethyl benzoylacetateHCID 108243-Methoxyaniline

Product 1

HCID 178487676HCID 178487676, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of m-anisidine (300 g, 2.44 mole) and ethyl benzoylacetate (234.2 g, 1.22 mole) in toluene (2.0 L) was added HCl (4.0 N in dioxane, 12.2 mL, 48.8 mmole). The resulting solution was refluxed for 6.5 hr using a Dean-Stark apparatus (about 56 ml of aqueous solution was collected). The mixture was cooled to rt, partitioned multiple times with aqueous HCl (10%, 3×500 mL), aqueous NaOH (1.0 N, 2×200 mL), water (3×200 mL), and the organic layer dried (MgSO4) and concentrated in vacuo to supply an oily residue (329.5 g). The crude product was heated in an oil bath (280° C.) for 80 min using a Dean-Stark apparatus (about 85 mL liquid was collected). The reaction mixture was cooled down to rt, the solid residue triturated with CH2Cl2 (400 mL), the resulting suspension filtered, and the filter cake washed with more CH2Cl2 (2×150 mL). The resulting solid was dried in vacuo (50° C.; 1 torr; 1 day) affording analytically pure 4-hydroxy-7-methoxy-2-phenylquinoline as a light brown solid (60.7 g, 20% overall). 1H NMR δ(DMSO): 3.86 (s, 3H), 6.26 (s, 1H), 6.94 (dd, J=9.0, 2.4 Hz, 1H), 7.21 (d, J=2.4 Hz, 1H), 7.55-7.62 (m, 3H), 7.80-7.84 (m, 2H), 8.00 (d, J=9.0 Hz, 1H), 11.54 (s, 1H); 13C NMR (DMSO-d6) δ: 55.38, 99.69, 107.07, 113.18, 119.22, 126.52, 127.17, 128.97, 130.34, 134.17, 142.27, 149.53, 161.92, 176.48. LC-MS (retention time: 1.26, method D), MS m/z 252 (M++1).

Workup

  1. temperatureThe resulting solution was refluxed for 6.5 hr
  2. customa Dean-Stark apparatus (about 56 ml of aqueous solution was collected)
  3. custompartitioned multiple times with aqueous HCl (10%, 3×500 mL), aqueous NaOH (1.0 N, 2×200 mL), water (3×200 mL)
  4. dry with materialthe organic layer dried (MgSO4)
  5. concentrationconcentrated in vacuo to supply an oily residue (329.5 g)
  6. temperatureThe crude product was heated in an oil bath (280° C.) for 80 min
  7. customa Dean-Stark apparatus (about 85 mL liquid was collected)
  8. temperatureThe reaction mixture was cooled down to rt
  9. customthe solid residue triturated with CH2Cl2 (400 mL)
  10. filtrationthe resulting suspension filtered
  11. washthe filter cake washed with more CH2Cl2 (2×150 mL)
  12. customThe resulting solid was dried in vacuo (50° C.; 1 torr; 1 day)

Sources & evidence

ORD record
ord-ba02126f44d1482bbe1ef306ae55f991
Source dataset
uspto-grants-2005_04
Patent number
US06878722B2

Reaction notes

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