Tetrahydrofuran → Ethyl 1-(1-cyclobutylethyl)-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate

HRID 469207Notes

Reaction equation

HRID 469207 reaction equation
Cl.[CH:2]1([CH:6]([NH2:8])[CH3:7])[CH2:5][CH2:4][CH2:3]1.C(N(CC)CC)C.C1COCC1.Cl[C:22]1[CH:39]=[C:38]([F:40])[C:37]([F:41])=[CH:36][C:23]=1[C:24]([C:26](=[CH:32]OCC)[C:27]([O:29][CH2:30][CH3:31])=[O:28])=[O:25]>O>[CH:2]1([CH:6]([N:8]2[C:22]3[C:23](=[CH:36][C:37]([F:41])=[C:38]([F:40])[CH:39]=3)[C:24](=[O:25])[C:26]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:32]2)[CH3:7])[CH2:5][CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 54163438Ethyl 2-(2-chloro-4,5-difluorobenzoyl)-3-ethoxyacrylateHCID 666369971-Cyclobutylethanamine hydrochloride

Product 1

HCID 66637155Ethyl 1-(1-cyclobutylethyl)-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylateYield 53.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

1.02 g of 1-cyclobutylethylamine hydrochloride and 1.05 ml of triethylamine were added under ice-cooling to a 15 ml THF solution of 2.0 g of ethyl 2-(2-chloro-4,5-difluorobenzoyl)-3-ethoxyacrylate, followed by overnight stirring at room temperature. Water was added to the resulting reaction mixture, followed by extraction with ether and washing with water and aqueous saturated sodium chloride. After drying over anhydrous magnesium sulfate, concentration under a reduced pressure was carried out. 315 mg of 55% sodium hydride was added under ice-cooling to a 30 ml dioxane solution of the resulting residue, followed by overnight stirring at 80° C. The reaction mixture was poured into 1 M hydrochloric acid, followed by extraction with chloroform and washing with water and aqueous saturated sodium chloride. After drying over anhydrous sodium sulfate and subsequent concentration under a reduced pressure, the resulting residue was purified by silica gel column chromatography to obtain 1.13 g of ethyl 1-(1-cyclobutylethyl)-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate.

Workup

  1. extractionfollowed by extraction with ether
  2. washwashing with water and aqueous saturated sodium chloride
  3. dry with materialAfter drying over anhydrous magnesium sulfate, concentration under a reduced pressure
  4. addition315 mg of 55% sodium hydride was added under ice-
  5. temperaturecooling to a 30 ml dioxane solution of the resulting residue
  6. waitfollowed by overnight
  7. stirringstirring at 80° C
  8. additionThe reaction mixture was poured into 1 M hydrochloric acid
  9. extractionfollowed by extraction with chloroform
  10. washwashing with water and aqueous saturated sodium chloride
  11. dry with materialAfter drying over anhydrous sodium sulfate and subsequent concentration under a reduced pressure
  12. customthe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-5b9148eb13cc4cad83e11ef5078dcc7e
Source dataset
uspto-grants-2014_01
Patent number
US08629126B2

Reaction notes

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