Sodium t-butoxide → 2-(4-Isopropylthiazol-2-YL)-7-methoxy-8-methylquinolin-4-OL

HRID 553442Notes

Reaction equation

HRID 553442 reaction equation
CC(C)([O-])C.[Na+].[C:7]([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([CH3:18])[C:11]=1[NH:19][C:20]([C:22]1[S:23][CH:24]=[C:25]([CH:27]([CH3:29])[CH3:28])[N:26]=1)=O)(=[O:9])[CH3:8]>C(O)(C)(C)C.C(OCC)(=O)C>[CH:27]([C:25]1[N:26]=[C:22]([C:20]2[CH:8]=[C:7]([OH:9])[C:10]3[C:11](=[C:12]([CH3:18])[C:13]([O:16][CH3:17])=[CH:14][CH:15]=3)[N:19]=2)[S:23][CH:24]=1)([CH3:29])[CH3:28]

Participants

5

Reactant 2

HCID 23676156Sodium t-butoxideHCID 53482122N-(6-Acetyl-3-methoxy-2-methylphenyl)-4-(propan-2-yl)-1,3-thiazole-2-carboxamide

Product 1

HCID 1784876922-(4-Isopropylthiazol-2-YL)-7-methoxy-8-methylquinolin-4-OLYield 108.3%

Reagents, catalysts & solvents 2

HCID 6386tert-ButanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

Sodium tert-butoxide (3.20 g, 28.6 mmol., 2.1 eq.) was added portion wise, at ambient temperature, to a solution of 1-acetyl-2-[(4-isopropyl-thiazol-2-yl)-carbonylamino]-3-methyl-4-methoxy-benzene (4.52 g, 13.6 mmol., 1.0 eq.) in dry tert-butanol (45 mL). The reaction mixture was stirred at 90° C. for 4 hours. LCMS analysis showed the reaction to be complete. The reaction mixture was left to cool to ambient temperature and then diluted with ethyl acetate (100 mL). The organic layer was washed with 1M aqueous potassium hydrogen sulphate (75 mL), water (50 mL), brine (50 mL), dried over sodium sulphate, filtered and the solvent removed under vacuum to give 4.63 g (99%) of the title compound as an off white solid. 1H NMR (500 MHz, CDCl3) δ ppm 9.59 (br. s, 1 H), 8.26 (d, J=9.16 Hz, 1 H), 7.10 (s, 1 H), 7.03 (d, J=9.16 Hz, 1 H), 6.77 (s, 1 H), 3.98 (s, 3 H), 3.20 (spt, J=6.87 Hz, 1 H), 2.43 (s, 3 H), 1.39 (d, J=7.02 Hz, 6 H). LC-MS: 95% (UV), tR 2.24 min, m/z [M+1]+ 315.15.

Workup

  1. customat ambient temperature
  2. customthe reaction
  3. waitThe reaction mixture was left
  4. temperatureto cool to ambient temperature
  5. washThe organic layer was washed with 1M aqueous potassium hydrogen sulphate (75 mL), water (50 mL), brine (50 mL)
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. customthe solvent removed under vacuum

Sources & evidence

ORD record
ord-6a3083256f2a4952bfd97e6bbe120442
Source dataset
uspto-grants-2011_11
Patent number
US08048862B2

Reaction notes

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