Potassium Carbonate → 4-[2-(2,6-Difluorophenyl)-4,5-dihydro-4-oxazolyl]-(4-fluorophenyl)methanone

HRID 964316Notes

Reaction equation

HRID 964316 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[O:10][CH2:11][CH:12]([C:14]2[CH:19]=[CH:18][C:17](I)=[CH:16][CH:15]=2)[N:13]=1.[F:21]C1C=CC(B(O)O)=CC=1.[C:31](=[O:34])([O-])[O-].[K+].[K+].[C]=O>C1(OC)C=CC=CC=1.[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:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[O:10][CH2:11][CH:12]([C:14]2([F:21])[CH:19]=[CH:18][C:17]([CH:31]=[O:34])=[CH:16][CH2:15]2)[N:13]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 11058111Oxazole, 2-(2,6-difluorophenyl)-4,5-dihydro-4-(4-iodophenyl)-HCID 178418416HCID 178418416, compound

Product 1

HCID 1317207194-[2-(2,6-Difluorophenyl)-4,5-dihydro-4-oxazolyl]-(4-fluorophenyl)methanoneYield 276.6%

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 7519AnisoleSolvent

Conditions

Temperature
80 °C

Procedure

The compound of Example 2 (0.5 g, 1.3 mmol) and 4-fluorophenyl boronic acid (0.27 g, 2 mmol) and potassium carbonate (fine mesh, 0.5 g, 0.4 mmol) were suspended in anisole (15 mL) and carbon monoxide was bubbled through the mixture for 5 min. Bis (triphenylphosphine) palladium chloride (0.03 g, 0.50 mmol) was added and the mixture was evacuated and carbon monoxide was released into the reaction by means of a balloon. The evacuation and carbon monoxide release was repeated and the reaction was heated to 80° C. under a carbon monoxide atmosphere for 3 h. The anisole was removed under reduced pressure and the residue was partitioned between diethylether (50 mL) and water (50 mL). The ether solution was dried over magnesium sulfate and evaporated under reduced pressure. The residue was subjected to silica gel chromatography with hexanes/ethyl acetate (5:1) as eluent to give the title compound (0.34 g) as a solid: m.p.: 105°-106° C. 1H NMR (CDCl3, 400 MHz) δ 7.9-7.0 (m,1H), 5.6 (m,1H), 4.9 (m,1H), 4.3 (m,1H).

Workup

  1. customcarbon monoxide was bubbled through the mixture for 5 min
  2. customthe mixture was evacuated
  3. customcarbon monoxide was released into the reaction by means of a balloon
  4. customThe anisole was removed under reduced pressure
  5. customthe residue was partitioned between diethylether (50 mL) and water (50 mL)
  6. dry with materialThe ether solution was dried over magnesium sulfate
  7. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-f16619bcf3ce43f49f45edebd89ac27f
Source dataset
uspto-grants-1998_06
Patent number
US05767281

Reaction notes

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