Ethyl Acetate → Ethyl 2,2-difluoro-2-(quinolin-6-yl)acetate

HRID 1921634Notes

Reaction equation

HRID 1921634 reaction equation
I[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2.Br[C:13]([F:20])([F:19])[C:14]([O:16][CH2:17][CH3:18])=[O:15].[Cl-].[NH4+].C(OCC)(=O)C>CS(C)=O.[Cu]>[CH2:17]([O:16][C:14](=[O:15])[C:13]([F:20])([F:19])[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2)[CH3:18]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 69585Ethyl bromodifluoroacetateHCID 203985536-Iodoquinoline

Product 1

HCID 28242385Ethyl 2,2-difluoro-2-(quinolin-6-yl)acetateYield 50.5%

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
55 °C

Procedure

To a suspension of 6-Iodoquinoline (10.2 g, 40 mmol) and Copper (O) (nanopowder, 5.59 g, 88 mmol) in dry DMSO (97 mL) was added 8.93 g (44 mmol) of ethyl bromodifluoroacetate. The reaction mixture was stirred under nitrogen at 55° C. for 15 hours. The reaction was allowed to reach room temperature and the mixture was poured over a solution of ammonium chloride. Ethyl acetate was added and the resulting mixture filtered over Celite. The organic layer was collected, dried (MgSO4), filtered and concentrated in vacuum. The crude mixture was chromatographied over silica gel with CH2Cl2 100% and CH2Cl2/MeOH:95/5 to yield 5.07 g of Difluoro-quinolin-6-yl-acetic acid ethyl ester as light yellow oil (50%).

Workup

  1. customto reach room temperature
  2. filtrationthe resulting mixture filtered over Celite
  3. customThe organic layer was collected
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuum

Sources & evidence

ORD record
ord-33f0174218554384857c604ca99b81d0
Source dataset
uspto-grants-2012_05
Patent number
US08173654B2

Reaction notes

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