Sodium Carbonate → N-[2-(2,2-difluoro-1,3-benzodioxol-4-yl)-4-methylphenyl]-2,2-dimethylpropanamide

HRID 1781244Notes

Reaction equation

HRID 1781244 reaction equation
Br[C:2]1[C:10]2[O:9][C:8]([F:12])([F:11])[O:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.B([C:16]1[CH:21]=[C:20]([CH3:22])[CH:19]=[CH:18][C:17]=1[NH:23][C:24](=[O:29])[C:25]([CH3:28])([CH3:27])[CH3:26])(O)O.C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C.CCCCCC>COCCOC.O.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:11][C:8]1([F:12])[O:7][C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([C:16]3[CH:21]=[C:20]([CH3:22])[CH:19]=[CH:18][C:17]=3[NH:23][C:24](=[O:29])[C:25]([CH3:27])([CH3:26])[CH3:28])[C:10]=2[O:9]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 27732974-Bromo-2,2-difluoro-1,3-benzodioxoleHCID 19045057N-(2-borono-4-methylphenyl)-2,2-dimethylpropanamideHCID 21226206Ethyl acetate hexane

Product 1

HCID 19045056N-[2-(2,2-difluoro-1,3-benzodioxol-4-yl)-4-methylphenyl]-2,2-dimethylpropanamide

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a mixture of the title compound of Step B (10.0 g, 42.2 mmol) and the title compound of Step A (4.96 g, 21.1 mmol) in ethylene glycol dimethyl ether (100 mL) were added a solution of sodium carbonate (4.47 g, 42.2 mmol) in water (25 mL) and bis(triphenylphosphine) palladium (II) chloride (740 mg, 1.05 mmol) at room temperature. The mixture was heated at reflux for 2 h and then allowed to come to room temperature. The solvent was removed under reduced pressure and the residue was suspended in water. The aqueous mixture was extracted with ethyl acetate three times. The organic extracts were dried (MgSO4), filtered, and concentrated under reduced pressure to obtain a brown liquid. Flash chromatography of the crude product on silica gel eluting with 1:6 ethyl acetate/hexane afforded the title compound of Step C, a compound of the invention, as a yellow oily solid (8 g, 55%). 1H NMR (CDCl3): δ1.12 (s,9H), 2.37 (s,3H), 7.1 (m,2H), 7.12 (s, 1H), 7.2 (t, 1H), 7.25 (m,1H), 7.3 (br s,1H), 7.9 (d, 1H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 2 h
  3. customto come to room temperature
  4. customThe solvent was removed under reduced pressure
  5. extractionThe aqueous mixture was extracted with ethyl acetate three times
  6. dry with materialThe organic extracts were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto obtain a brown liquid

Sources & evidence

ORD record
ord-d18919271ba346f0943598126ca972e9
Source dataset
uspto-grants-1997_05
Patent number
US05633218

Reaction notes

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