Hydrochloric Acid → HCID 23159833, compound

HRID 2110883Notes

Reaction equation

HRID 2110883 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=1)[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][C:15]([O:17]C)=[O:16])=[CH:9][CH:8]=1.[C:22]1([CH:28]2[O:33][CH2:32][CH2:31][NH:30][CH2:29]2)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[OH-].[Na+].Cl>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].O1CCCC1.CO.C1(C)C=CC=CC=1>[C:22]1([CH:28]2[O:33][CH2:32][CH2:31][N:30]([C:2]3[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=3)[CH2:5][O:6][C:7]3[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][C:15]([OH:17])=[O:16])=[CH:9][CH:8]=3)[CH2:29]2)[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 14798Sodium HydroxideHCID 911012-PhenylmorpholineHCID 634876Binap, (A+-)-HCID 23136270Methyl 4-[(3-bromophenyl)methoxy]benzenepropanoate

Product 1

HCID 23159833HCID 23159833, compoundYield 50.1%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of methyl 3-{4-[(3-bromobenzyl)oxy]phenyl}propanoate (0.3 g, 0.86 mmol), 2-phenylmorpholine (0.21 g, 1.29 mmol), tris(dibenzylideneacetone)dipalladium(0) (31 mg, 34 μmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (32 mg, 52 μmol), cesium carbonate (0.39 g, 1.2 mmol) and toluene (6.0 mL) was stirred under a nitrogen atmosphere at 80° C. for 16 hr. After cooling, the reaction mixture washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give an oil. Then, to a mixture of the obtained oil, methanol (4.0 mL) and tetrahydrofuran (6.0 mL) was added 1N aqueous sodium hydroxide solution (2.0 mL) with stirring at room temperature, and the mixture was stirred at the same temperature for 2 hr. The reaction mixture was adjusted to pH 7 with 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=2/1-hexane/ethyl acetate=1/2) to give the title compound (0.18 g, yield 36%) as a yellow oil.

Workup

  1. temperatureAfter cooling
  2. washthe reaction mixture washed with water and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customto give an oil
  6. stirringwith stirring at room temperature
  7. stirringthe mixture was stirred at the same temperature for 2 hr
  8. extractionextracted with ethyl acetate
  9. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=2/1-hexane/ethyl acetate=1/2)

Sources & evidence

ORD record
ord-a641d3e76b3e4732ac0735981fd47b81
Source dataset
uspto-grants-2009_04
Patent number
US07517910B2

Reaction notes

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