Water → 4-Oxo-3-[4-(tetrahydropyran-2-yloxy)-phenyl]-butyric acid methyl ester

HRID 2070575Notes

Reaction equation

HRID 2070575 reaction equation
[CH3:1][O:2][C:3](=[O:22])[CH2:4][CH:5]([C:9]1[CH:14]=[CH:13][C:12]([O:15][CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][O:17]2)=[CH:11][CH:10]=1)/[CH:6]=C\C.[O:23]1CCOCC1.O.N1C(C)=CC=CC=1C>[Os](=O)(=O)(=O)=O.C(OCC)(=O)C.C(O)(C)(C)C>[CH3:1][O:2][C:3](=[O:22])[CH2:4][CH:5]([C:9]1[CH:14]=[CH:13][C:12]([O:15][CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][O:17]2)=[CH:11][CH:10]=1)[CH:6]=[O:23]

Participants

8

Reactant 4

HCID 962WaterHCID 79372,6-LutidineHCID 312751,4-DioxaneHCID 57771537(Z)-3-[4-(tetrahydropyran-2-yloxy)-phenyl]-hex-4-enoic acid methyl ester

Product 1

HCID 577714374-Oxo-3-[4-(tetrahydropyran-2-yloxy)-phenyl]-butyric acid methyl ester

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 6386tert-ButanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (Z)-3-[4-(tetrahydropyran-2-yloxy)-phenyl]-hex-4-enoic acid methyl ester (3.83 g) obtained in Step 2 in a mixed solvent of dioxane (60 mL)-water (15 mL) was added 2,6-lutidine (2.8 mL). Then, to this was added dropwise a tert-butanol solution of osmium tetroxide (5 mg/mL, 12 mL) over 5 minutes, followed by stirring the reaction mixture at room temperature for 3 minutes. Then, to the reaction mixture was added dropwise-aqueous-sodium periodate solution (10.3 g/25 mL) over 7 minutes, followed by stirring the reaction mixture at room temperature for 2 hours. After addition of ethyl acetate to the reaction mixture, the organic layer was separated. The organic layer was washed successively with 1N aqueous hydrochloric acid solution, water, saturated aqueous sodium bicarbonate solution, saturated aqueous sodium thiosulfate solution and saturated brine, dried and concentrated. The residue was purified by column chromatography on silica gel (ethyl acetate:hexane (volume ratio)=1:4 to 1:3) to give 4-oxo-3-[4-(tetrahydropyran-2-yloxy)-phenyl]-butyric acid methyl ester (2.59 g).

Workup

  1. stirringby stirring the reaction mixture at room temperature for 2 hours
  2. customthe organic layer was separated
  3. washThe organic layer was washed successively with 1N aqueous hydrochloric acid solution, water, saturated aqueous sodium bicarbonate solution, saturated aqueous sodium thiosulfate solution and saturated brine
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography on silica gel (ethyl acetate:hexane (volume ratio)=1:4 to 1:3)

Sources & evidence

ORD record
ord-1024a37e016e41d789f158cebaa91ae9
Source dataset
uspto-grants-2012_10
Patent number
US08299296B2

Reaction notes

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