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

HRID 2178212Notes

Reaction equation

HRID 2178212 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:18]=[C:17]3[C:12]([CH2:13][CH2:14][CH2:15][N:16]3[C:19](=[O:21])[CH3:20])=[CH:11][CH:10]=2)O1.Br[C:24]1[S:25][C:26]([Cl:34])=[C:27]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[N: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:19]([N:16]1[C:17]2[C:12](=[CH:11][CH:10]=[C:9]([C:24]3[S:25][C:26]([Cl:34])=[C:27]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[N:28]=3)[CH:18]=2)[CH2:13][CH2:14][CH2:15]1)(=[O:21])[CH3:20]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 433294Lithium ChlorideHCID 11196524Ethyl 2-bromo-5-chloro-1,3-thiazole-4-carboxylateHCID 594187501-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-1(2H)-yl)ethanone

Product 1

HCID 59418737Ethyl 2-(1-acetyl-1,2,3,4-tetrahydroquinolin-7-yl)-5-chlorothiazole-4-carboxylateYield 34%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

To 1-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-1(2H)-yl)ethanone (1G) (1.24 g, 4.12 mmol), ethyl 2-bromo-5-chlorothiazole-4-carboxylate (1I) (1.12 g, 4.12 mmol), lithium chloride (0.52 g, 12.4 mmol), tetrakis(triphenylphosphine)palladium (0.476 g, 0.412 mmol), and cesium carbonate (4.03 g, 12.4 mmol) was added 1,4-dioxane (30 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. To the crude residue was added EtOAc and water. The layers were separated and the aqueous layer was extracted with EtOAc and 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 0.505 g (34%) of the desired product ethyl 2-(1-acetyl-1,2,3,4-tetrahydroquinolin-7-yl)-5-chlorothiazole-4-carboxylate (1J): LC/MS (APCI): m/z 365.3 (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. additionTo the crude residue was added EtOAc and water
  7. customThe layers were separated
  8. extractionthe aqueous layer was extracted with EtOAc
  9. washthe combined organic extracts were washed sequentially with water, brine
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. 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-10e0ba7a2dfa46988872f7d991d07312
Source dataset
uspto-grants-2015_06
Patent number
US09067928B2

Reaction notes

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