Hydrochloric Acid → Phenylacetic Acid

HRID 2375206Notes

Reaction equation

HRID 2375206 reaction equation
[C:1]1([CH2:7][C:8]([O:10]C2CCCCO2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.BrCCCCCBr.[H-].[Na+].Cl>CN(C)P(=O)(N(C)C)N(C)C.O1CCOCC1.O.C(OCC)(=O)C>[C:1]1([CH2:7][C:8]([OH:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 81001,5-DibromopentaneHCID 24758Sodium hydrideHCID 58611841HCID 58611841, compound

Product 1

HCID 999Phenylacetic AcidYield 71.4%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 12679HexamethylphosphoramideSolventHCID 312751,4-DioxaneSolvent

Procedure

The crude tetrahydro-2H-pyran-2-yl 2-phenylacetate (E5) (0.581 g, 4.26 mmol)) and 1,5-dibromopentane (1.474 g, 6.41 mmol) were dissolved in dry hexamethylphosphoric triamide (6 ml) and the mixture was cooled in an ice bath. To the cooled solution 60% suspension of NaH in mineral oil (0.507 g, 12.67 mmol) was added and the reaction mixture was stirred at ice bath temperature for 15 minutes and at room temperature for 5 hours. The reaction mixture was diluted with dioxane (20 ml) and water (15 ml), and the pH of the reaction medium was brought to pH 1 with conc. HCl (3 ml). The reaction mixture was stirred for 20 minutes and poured into ethyl acetate (75 ml). The organic layer was washed with a mixture of 2 N HCl and brine, 1:1 (2×50 ml), brine (50 ml), and dried (Na2SO4). The solvents were evaporated and the residue was chromatographed on silicagel (50 g) with benzene-ethyl acetate-acetic acid (9:1:0.1) as eluent to give a crude product. The product was re-chromatographed on silicagel (50 g) with petroleum ether-ethyl acetate-acetic acid (8:2:0.1) as eluent to give the title compound (0.414 g, 47% based on E4) as a white solid. 1H NMR (CDCl3, HMDSO) δ: 1.04-2.01 (8H, m); 2.19-2.62 (2H, m); 7.09-7.55 (5H, m), 10.29 (1H, br s).

Workup

  1. temperaturethe mixture was cooled in an ice bath
  2. additionwas added
  3. waitat room temperature for 5 hours
  4. stirringThe reaction mixture was stirred for 20 minutes
  5. washThe organic layer was washed with a mixture of 2 N HCl and brine, 1:1 (2×50 ml), brine (50 ml)
  6. dry with materialdried (Na2SO4)
  7. customThe solvents were evaporated
  8. customthe residue was chromatographed on silicagel (50 g) with benzene-ethyl acetate-acetic acid (9:1:0.1) as eluent
  9. customto give a crude product
  10. customThe product was re-chromatographed on silicagel (50 g) with petroleum ether-ethyl acetate-acetic acid (8:2:0.1) as eluent

Sources & evidence

ORD record
ord-ac16137a577a4522b8a53c568870e776
Source dataset
uspto-grants-2008_12
Patent number
US07465719B2

Reaction notes

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