Sodium Hydroxide → 2-(4-Chloro-7-methoxy-8-methylquinolin-2-yl)-4-isopropylthiazole

HRID 553443Notes

Reaction equation

HRID 553443 reaction equation
[CH:1]([C:4]1[N:5]=[C:6]([C:9]2[CH:18]=[C:17](O)[C:16]3[C:11](=[C:12]([CH3:22])[C:13]([O:20][CH3:21])=[CH:14][CH:15]=3)[N:10]=2)[S:7][CH:8]=1)([CH3:3])[CH3:2].P(Cl)(Cl)([Cl:25])=O.[OH-].[Na+]>>[CH:1]([C:4]1[N:5]=[C:6]([C:9]2[CH:18]=[C:17]([Cl:25])[C:16]3[C:11](=[C:12]([CH3:22])[C:13]([O:20][CH3:21])=[CH:14][CH:15]=3)[N:10]=2)[S:7][CH:8]=1)([CH3:3])[CH3:2]

Participants

4

Reactant 3

HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 1784876922-(4-Isopropylthiazol-2-YL)-7-methoxy-8-methylquinolin-4-OL

Product 1

HCID 513586512-(4-Chloro-7-methoxy-8-methylquinolin-2-yl)-4-isopropylthiazoleYield 91%

Conditions

Temperature
90 °C

Procedure

2-(4-isopropylthiazol-2-yl)-4-hydroxy-7-methoxy-8-methyl-quinoline (4.63 g, 13.6 mmol., 1.0 eq.) was charged into a 100 mL round bottom flask. Phosphorous oxychloride (45 mL) was added and the reaction mixture stirred at 90° C. for 3 hours. Monitoring the reaction mixture by 1H NMR showed full consumption of the starting material. The reaction mixture was left to cool to ambient temperature and the solvent removed under vacuum. The residue was diluted with ethyl acetate (80 mL) and the reaction mixture cooled to 0° C. 2M aqueous sodium hydroxide solution was added portion wise until the pH of the aqueous phase was 14 (stir reaction mixture for 1 min between every NaOH addition). The two layers were separated and the organic layer was further washed with water (50 mL) and brine (50 mL). The organic layer was dried over sodium sulphate, filtered and the solvent removed under vacuum to give 4.11 g (91%) of the title compound as a pale brown solid. 1H NMR (500 MHz, CDCl3) δ ppm 8.28 (s, 1 H), 8.09 (d, J=9.16 Hz, 1 H), 7.38 (d, J=9.16 Hz, 1 H), 7.06 (s, 1 H), 4.02 (s, 3 H), 3.20 (spt, J=6.87 Hz, 1 H), 2.73 (s, 3 H), 1.40 (d, J=6.87 Hz, 6 H).

Workup

  1. customconsumption of the starting material
  2. waitThe reaction mixture was left
  3. temperatureto cool to ambient temperature
  4. customthe solvent removed under vacuum
  5. additionThe residue was diluted with ethyl acetate (80 mL)
  6. temperaturethe reaction mixture cooled to 0° C
  7. addition2M aqueous sodium hydroxide solution was added portion wise until the pH of the aqueous phase
  8. stirringstir
  9. customreaction mixture for 1 min
  10. customThe two layers were separated
  11. washthe organic layer was further washed with water (50 mL) and brine (50 mL)
  12. dry with materialThe organic layer was dried over sodium sulphate
  13. filtrationfiltered
  14. customthe solvent removed under vacuum

Sources & evidence

ORD record
ord-8b7e06df434842ab9e117ecf99b5902e
Source dataset
uspto-grants-2011_11
Patent number
US08048862B2

Reaction notes

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