Cesium carbonate → 4-(2',6'-Dimethoxyphenyl)-2-benzyloxy-benzoic acid, benzyl ester

HRID 2185942Notes

Reaction equation

HRID 2185942 reaction equation
[CH2:1]([O:8][C:9]1[CH:24]=[C:23](Cl)[CH:22]=[CH:21][C:10]=1[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:26][O:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([O:34][CH3:35])[C:29]=1B(O)O.C([O-])([O-])=O.[Cs+].[Cs+].P(C(C)(C)C)(C(C)(C)C)C(C)(C)C>C1COCC1.CCOCC.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:26][O:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([O:34][CH3:35])[C:29]=1[C:23]1[CH:22]=[CH:21][C:10]([C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:12])=[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH:24]=1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 2734343(2,6-Dimethoxyphenyl)boronic acidHCID 66989997Benzyl 2-(benzyloxy)-4-chlorobenzoate

Product 1

HCID 867581364-(2',6'-Dimethoxyphenyl)-2-benzyloxy-benzoic acid, benzyl ester

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of of 2-benzyloxy-4-chlorobenzoic acid, benzyl ester (1.0)g, 2.83 mmol), 2,6-dimethoxybenzene boronic acid (0.62 g, 3.4 mmol), Pd2dba3 (0.26 g, 0.28 mmol), Cs2CO3 (1.38 g, 4.2 mmol), and t-Bu3P (0.12 g, 0.57 mmol) was dissolved in 8.0 mL of THF and warmed to reflux for 24 h. The reaction mixture was cooled, diluted with Et2O and H2O and the layers were separated. The organic layer was successively washed with 1N HCl (2×100 ml), saturated NaHCO3 solution (2×50 ml), brine (1×50 ml), dried over anhydrous MgSO4 and concentrated. The residue was purified by flash column chromatography on silica gel eluted with a gradient of 25-50% Et2O in hexanes to give 4-(2′,6′-dimethoxyphenyl)-2-benzyloxy-benzoic acid, benzyl ester as a pale yellow oil.

Workup

  1. temperaturewarmed
  2. temperatureto reflux for 24 h
  3. temperatureThe reaction mixture was cooled
  4. customthe layers were separated
  5. washThe organic layer was successively washed with 1N HCl (2×100 ml), saturated NaHCO3 solution (2×50 ml), brine (1×50 ml)
  6. dry with materialdried over anhydrous MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified by flash column chromatography on silica gel
  9. washeluted with a gradient of 25-50% Et2O in hexanes

Sources & evidence

ORD record
ord-cb8a8c44a1f24836a5a083becb22ce4f
Source dataset
uspto-grants-2002_06
Patent number
US06403584B1

Reaction notes

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