Cesium carbonate → Ethyl 2-(1-acetyl-1,2,3,4-tetrahydroquinolin-7-yl)-5-(4-methoxyphenyl)thiazole-4-carboxylate

HRID 2178213Notes

Reaction equation

HRID 2178213 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].[CH3:25][O:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.[Cl-].[Li+].C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.O1CCOCC1>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]3[S:15][C:16]([C:30]4[CH:31]=[CH:32][C:27]([O:26][CH3:25])=[CH:28][CH:29]=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

8

Reactant 4

HCID 10796Cesium carbonateHCID 201262(4-Methoxyphenyl)boronic acidHCID 433294Lithium ChlorideHCID 59418737Ethyl 2-(1-acetyl-1,2,3,4-tetrahydroquinolin-7-yl)-5-chlorothiazole-4-carboxylate

Product 1

HCID 59418743Ethyl 2-(1-acetyl-1,2,3,4-tetrahydroquinolin-7-yl)-5-(4-methoxyphenyl)thiazole-4-carboxylateYield 90%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To ethyl 2-(1-acetyl-1,2,3,4-tetrahydroquinolin-7-yl)-5-chlorothiazole-4-carboxylate (1J) (0.450 g, 1.23 mmol), 4-methoxyphenylboronic acid (0.281 g, 1.85 mmol), lithium chloride (0.157 g, 3.70 mmol), tetrakis(triphenylphosphine)palladium (0) (0.142 g, 0.12 mmol), and cesium carbonate (1.2 g, 3.70 mmol) was added 1,4-dioxane (20 mL) and water (10 mL). Nitrogen was bubbled through the reaction mixture for 5 minutes. The reaction mixture was heated to 100° C. and stirred overnight. The reaction mixture was cooled to rt, diluted with EtOAc, filtered through Celite, 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 0.483 g (90%) of the desired product ethyl 2-(1-acetyl-1,2,3,4-tetrahydroquinolin-7-yl)-5-(4-methoxyphenyl)thiazole-4-carboxylate (1K): LC/MS (APCI): m/z 436.8 (M+H).

Workup

  1. customNitrogen was bubbled through the reaction mixture for 5 minutes
  2. temperatureThe reaction mixture was cooled to rt
  3. additiondiluted with EtOAc
  4. filtrationfiltered through Celite
  5. concentrationconcentrated under reduced pressure
  6. 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-61c7806560e14ea6a553802be47d103f
Source dataset
uspto-grants-2015_06
Patent number
US09067928B2

Reaction notes

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