Methanol → 5-(4-Methoxyphenyl)-2-(1,2,3,4-tetrahydroquinolin-7-yl)thiazole-4-carboxylic acid

HRID 1896563Notes

Reaction equation

HRID 1896563 reaction equation
C([N:4]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]3[S:15][C:16]([C:24]4[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=4)=[C:17]([C:19]([O:21]CC)=[O:20])[N:18]=3)[CH:12]=2)[CH2:7][CH2:6][CH2:5]1)(=O)C.[OH-].[K+].CO>O>[CH3:31][O:30][C:27]1[CH:28]=[CH:29][C:24]([C:16]2[S:15][C:14]([C:11]3[CH:12]=[C:13]4[C:8]([CH2:7][CH2:6][CH2:5][NH:4]4)=[CH:9][CH:10]=3)=[N:18][C:17]=2[C:19]([OH:21])=[O:20])=[CH:25][CH:26]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 14797Potassium HydroxideHCID 59418743Ethyl 2-(1-acetyl-1,2,3,4-tetrahydroquinolin-7-yl)-5-(4-methoxyphenyl)thiazole-4-carboxylate

Product 1

HCID 594187575-(4-Methoxyphenyl)-2-(1,2,3,4-tetrahydroquinolin-7-yl)thiazole-4-carboxylic acidYield 86%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
55 °C

Procedure

To ethyl 2-(1-acetyl-1,2,3,4-tetrahydroquinolin-7-yl)-5-(4-methoxyphenyl)thiazole-4-carboxylate (1K) (0.483 g, 1.11 mmol) and KOH (1.24 g, 22.1 mmol) was added MeOH (10 mL) and water (45 mL). The reaction mixture was allowed to heat to 55° C. and stirred 48 hours. The reaction was monitored by LCMS. To the reaction mixture was added (0.5 g, 8.9 mmol). The reaction mixture was allowed to heat to 55° C. and stirred for 24 hours. The reaction mixture was cooled to rt and concentrated under reduced pressure. To the crude residue was added EtOAc and water. The layers were separated and the aqueous extract was acidified to ˜pH6 with 1N HCl and extracted with EtOAc. The combined organic extracts were washed sequentially with water, brine, dried over MgSO4, filtered, and concentrated under reduced pressure to provide 0.350 g (86%) of the desired product 544-methoxyphenyl)-2-(1,2,3,4-tetrahydroquinolin-7-yl)thiazole-4-carboxylic acid (1L): LC/MS (APCI): m/z 367.0 (M+H).

Workup

  1. additionTo the reaction mixture was added (0.5 g, 8.9 mmol)
  2. temperatureto heat to 55° C.
  3. stirringstirred for 24 hours
  4. temperatureThe reaction mixture was cooled to rt
  5. concentrationconcentrated under reduced pressure
  6. additionTo the crude residue was added EtOAc and water
  7. customThe layers were separated
  8. extractionthe aqueous extract
  9. extractionextracted with EtOAc
  10. washThe combined organic extracts were washed sequentially with water, brine
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9f64038d4a84405a9975fdb6041a96f0
Source dataset
uspto-grants-2013_08
Patent number
US08518970B2

Reaction notes

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