Cesium carbonate → Ethyl 2-(4-chloro-3-methylphenyl)-1,3-oxazole-4-carboxylate

HRID 508157Notes

Reaction equation

HRID 508157 reaction equation
I[C:2]1[O:3][CH:4]=[C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[N:6]=1.[Cl:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][C:14]=1[CH3:22].C(=O)([O-])[O-].[Cs+].[Cs+]>CN1CCCC1=O.O.C(OCC)(=O)C>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([C:2]2[O:3][CH:4]=[C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[N:6]=2)=[CH:15][C:14]=1[CH3:22]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 3786632(4-Chloro-3-methylphenyl)boronic acidHCID 46910517Ethyl 2-iodooxazole-4-carboxylate

Product 1

HCID 58284444Ethyl 2-(4-chloro-3-methylphenyl)-1,3-oxazole-4-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
50 °C

Procedure

385 mg (1.44 mmol) of the compound from Example 25A and 319 mg (1.87 mmol) of 4-chloro-3-methylphenylboronic acid are initially charged in 12.7 ml of dry N-methyl-2-pyrrolidone. 105 mg (0.14 mmol) of bis(diphenylphosphino)ferrocenepalladium(II) chloride, 0.33 ml water and 940 mg (2.88 mmol) of cesium carbonate are then added. The reaction mixture is stirred at 50° C. for 4 h. The mixture is then cooled to RT, and 20 ml of ethyl acetate and 10 ml of water are added. The aqueous phase is extracted twice with in each case 20 ml of ethyl acetate. The combined organic phases are washed once with 10 ml of sat. aqueous sodium chloride solution and dried over magnesium sulfate. After filtration, the solvent is removed on a rotary evaporator. The residue is purified by preparative HPLC (column: YMC GEL ODS-AQ S-5/15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5).

Workup

  1. temperatureThe mixture is then cooled to RT
  2. extractionThe aqueous phase is extracted twice with in each case 20 ml of ethyl acetate
  3. washThe combined organic phases are washed once with 10 ml of sat. aqueous sodium chloride solution
  4. dry with materialdried over magnesium sulfate
  5. filtrationAfter filtration
  6. customthe solvent is removed on a rotary evaporator
  7. customThe residue is purified by preparative HPLC (column: YMC GEL ODS-AQ S-5/15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5)

Sources & evidence

ORD record
ord-1849e622ced84b58892227400e62e57c
Source dataset
uspto-grants-2015_08
Patent number
US09095582B2

Reaction notes

Loading…