Cesium carbonate → Methyl 2-(4-(benzyloxy)-3,5-dichlorophenylamino)benzoate

HRID 883818Notes

Reaction equation

HRID 883818 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:7]([O:14][C:15]1[C:21]([Cl:22])=[CH:20][C:18]([NH2:19])=[CH:17][C:16]=1[Cl:23])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Br[C:71]1[CH:80]=[CH:79][CH:78]=[CH:77][C:72]=1[C:73]([O:75][CH3:76])=[O:74]>C1(C)C=CC=CC=1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:7]([O:14][C:15]1[C:16]([Cl:23])=[CH:17][C:18]([NH:19][C:71]2[CH:80]=[CH:79][CH:78]=[CH:77][C:72]=2[C:73]([O:75][CH3:76])=[O:74])=[CH:20][C:21]=1[Cl:22])[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 11894Methyl 2-bromobenzoateHCID 634876Binap, (A+-)-HCID 185431714-(Benzyloxy)-3,5-dichloroaniline

Product 1

HCID 59509768Methyl 2-(4-(benzyloxy)-3,5-dichlorophenylamino)benzoateYield 94%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

Cesium carbonate (5.98 g, 19 mmol) was added to a stirring solution of 4-(benzyloxy)-3,5-dichloroaniline (5.27 g [crude from previous step], 19 mmol) in toluene. Rac-BINAP (0.6 g, 7.5 mol %) and methyl 2-bromobenzoate (1.84 ml 13 mmol,) were added. Palladium(II) acetate (0.147 g, 5 mol %) was added and the mixture heated to 100° C. After 12 h the mixture was cooled to room temperature, diluted with ethyl acetate (100 mL), washed with pH 7 buffer solution (50 mL) and extracted with ethyl acetate (100 mL). The combined organic layers were dried (MgSO4), filtered and concentrated in vacuo to afford a residue that was purified by column chromatography (3:1, petroleum ether/dichloromethane) to afford methyl 2-(4-(benzyloxy)-3,5-dichlorophenylamino)benzoate as a white solid (94% yield).

Workup

  1. temperatureAfter 12 h the mixture was cooled to room temperature
  2. washwashed with pH 7 buffer solution (50 mL)
  3. extractionextracted with ethyl acetate (100 mL)
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto afford a residue that
  8. customwas purified by column chromatography (3:1, petroleum ether/dichloromethane)

Sources & evidence

ORD record
ord-980be7ca4be946f0bca7a4c36ce8724a
Source dataset
uspto-grants-2012_08
Patent number
US08236984B2

Reaction notes

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