Sodium Carbonate → N-[2-(2,2-Difluoro-1,3-benzodioxol-5-yl)-4-methylphenyl]acetamide

HRID 1781243Notes

Reaction equation

HRID 1781243 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([CH3:11])=[O:10])=[C:4](Br)[CH:3]=1.[F:13][C:14]1([F:26])[O:18][C:17]2[CH:19]=[CH:20][C:21](B(O)O)=[CH:22][C:16]=2[O:15]1.C(=O)([O-])[O-].[Na+].[Na+]>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:26][C:14]1([F:13])[O:15][C:16]2[CH:22]=[CH:21][C:20]([C:4]3[CH:3]=[C:2]([CH3:1])[CH:7]=[CH:6][C:5]=3[NH:8][C:9](=[O:10])[CH3:11])=[CH:19][C:17]=2[O:18]1

Participants

7

Reactant 3

HCID 10340Sodium Carbonate2×HCID 69200Acetamide, N-(2-bromo-4-methylphenyl)-HCID 17750030(2,2-Difluoro-1,3-dioxaindan-5-yl)boronic acid2×

Product 1

HCID 19045055N-[2-(2,2-Difluoro-1,3-benzodioxol-5-yl)-4-methylphenyl]acetamide

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent3×HCID 80711,2-DimethoxyethaneSolvent

Procedure

To a mixture of 2-bromo-4-methylacetanilide (1.5 g, 6.6 mmol) and the title compound of Step B (2.0 g, 9.9 mmol) in ethylene glycol dimethyl ether (20 mL) were added a solution of sodium carbonate (2.1 g, 20 mmol) in water (20 mL) and bis(triphenylphosphine) palladium (II) chloride (230 mg, 0.33 mmol). The mixture was heated at reflux overnight, and then additional title compound of Step B (1.0 g, 4.9 mmol) and sodium carbonate (1.0 g, 9.4 mmol) as a solution in water (approximately 10 mL) were added. The mixture was heated at reflux an additional 6 h and then allowed to come to room temperature. The mixture was poured into water and the aqueous mixture was extracted with ethyl acetate four times. The combined organic extracts were dried (MgSO4), filtered and concentrated under reduced pressure to give a dark-brown oil. The oil was purified by flash chromatography on silica gel, eluting with 1:4 ethyl acetate/hexane to afford the title compound of Step C, a compound of the invention, as a light brown solid melting at 105°-107° C. (205 mg, 10%). 1H NMR (CD3COCD3): δ1.95 (s,3H), 2.36 (s,3H), 7.2(m,2H), 7.25(m,3H), 7.8(m, 1H), 8.55(br s, 1H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux overnight
  3. temperatureThe mixture was heated
  4. temperatureat reflux an additional 6 h
  5. customto come to room temperature
  6. extractionthe aqueous mixture was extracted with ethyl acetate four times
  7. dry with materialThe combined organic extracts were dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto give a dark-brown oil
  11. customThe oil was purified by flash chromatography on silica gel
  12. washeluting with 1:4 ethyl acetate/hexane

Sources & evidence

ORD record
ord-3059335a2ed14734ab0b8b6bd679db34
Source dataset
uspto-grants-1997_05
Patent number
US05633218

Reaction notes

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