Phenol → Ethyl 2-(1-acetyl-1,2,3,4-tetrahydroquinolin-7-yl)-5-phenoxythiazole-4-carboxylate

HRID 2178224Notes

Reaction equation

HRID 2178224 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]3[S:15][C:16](Cl)=[C:17]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[N:18]=3)[CH:12]=2)[CH2:7][CH2:6][CH2:5]1)(=[O:3])[CH3:2].[C:25]1([OH:31])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.[OH-].[K+].CN(C=O)C>CCOC(C)=O.O>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]3[S:15][C:16]([O:31][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[C:17]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[N:18]=3)[CH:12]=2)[CH2:7][CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 996PhenolHCID 6228DimethylformamideHCID 14797Potassium HydroxideHCID 59418737Ethyl 2-(1-acetyl-1,2,3,4-tetrahydroquinolin-7-yl)-5-chlorothiazole-4-carboxylate

Product 1

HCID 59418766Ethyl 2-(1-acetyl-1,2,3,4-tetrahydroquinolin-7-yl)-5-phenoxythiazole-4-carboxylateYield 72%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To ethyl 2-(1-acetyl-1,2,3,4-tetrahydroquinolin-7-yl)-5-chlorothiazole-4-carboxylate (1J) (0.250 g, 0.69 mmol), phenol (0.129 g, 1.4 mmol), and KOH (0.284 g, 2.1 mmol) was added DMF (10 mL). The reaction mixture was allowed to heat to 70° C. for 72 hours. The reaction mixture was cooled to rt and diluted with EtOAc and water. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic extracts were washed sequentially with water, brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The crude residue was purified by column chromatography on silica gel eluting with a gradient of 0 to 80% EtOAc in hexanes to provide 0.208 g (72%) ethyl 2-(1-acetyl-1,2,3,4-tetrahydroquinolin-7-yl)-5-phenoxythiazole-4-carboxylate (21A): LC/MS (APCI): m/z 424.0 (M+H).

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc
  4. washThe combined organic extracts were washed sequentially with water, brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude residue was purified by column chromatography on silica gel eluting with a gradient of 0 to 80% EtOAc in hexanes

Sources & evidence

ORD record
ord-f61101924ab942c294866ba7e0f0e2f7
Source dataset
uspto-grants-2015_06
Patent number
US09067928B2

Reaction notes

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