Cesium carbonate → HCID 67490962, compound

HRID 1917424Notes

Reaction equation

HRID 1917424 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@:9]12[CH2:16][CH2:15][C:14]([F:18])([F:17])[C@@H:13]1[CH2:12][NH:11][CH2:10]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:20]1[C:29]([CH3:30])=[C:28]2[C:23]([C:24](=[O:40])[C:25]([C:35]([O:37][CH2:38][CH3:39])=[O:36])=[CH:26][N:27]2[C@@H:31]2[CH2:33][C@@H:32]2[F:34])=[CH:22][C:21]=1[F:41].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]([O:5][C:6]([NH:8][C@@:9]12[CH2:16][CH2:15][C:14]([F:18])([F:17])[C@@H:13]1[CH2:12][N:11]([C:20]1[C:29]([CH3:30])=[C:28]3[C:23]([C:24](=[O:40])[C:25]([C:35]([O:37][CH2:38][CH3:39])=[O:36])=[CH:26][N:27]3[C@@H:31]3[CH2:33][C@@H:32]3[F:34])=[CH:22][C:21]=1[F:41])[CH2:10]2)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 67490917HCID 67490917, compoundHCID 67490955HCID 67490955, compound

Product 1

HCID 67490962HCID 67490962, compoundYield 69.8%

Reagents, catalysts & solvents 4

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of (1S,5R)-1-tert-butoxycarbonylamino-6,6-difluoro-3-azabicyclo[3.3.0]octane (318 mg, 1.21 mmol), ethyl 7-bromo-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylate (426 mg, 1.10 mmol), 1,1′-bis(diphenylphosphino)ferrocene (183 mg, 0.331 mmol), tris(dibenzylideneacetone)dipalladium(0) (101 mg, 0.110 mmol) and cesium carbonate (718 mg, 2.20 mmol) in dioxane (5.51 mL) was stirred at room temperature for 30 minutes, and at 100° C. for 11 hours under argon atmosphere. The mixture was diluted with water, and extracted with ethyl acetate and chloroform (3×). The combined organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel flush column chromatography (ethyl acetate/hexane=10:90→50:50→67:33→ethyl acetate) to afford 436 mg of the title compound as a pale yellow foam.

Workup

  1. waitat 100° C. for 11 hours under argon atmosphere
  2. extractionextracted with ethyl acetate and chloroform (3×)
  3. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  4. distillationthe solvent was distilled off under reduced pressure
  5. customThe residue was purified by silica gel
  6. customflush column chromatography (ethyl acetate/hexane=10:90→50:50→67:33→ethyl acetate)

Sources & evidence

ORD record
ord-6aa229b28acc4cc59684913a1b53955f
Source dataset
uspto-grants-2013_12
Patent number
US08618094B2

Reaction notes

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