2-Phenylethanol → 4-[4-(2-Hydroxyethyl)phenyl]-4-oxo-butyric acid methyl ester

HRID 1751814Notes

Reaction equation

HRID 1751814 reaction equation
[CH2:1]([OH:9])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:10][O:11][C:12](=[O:18])[CH2:13][CH2:14][C:15](Cl)=[O:16].[Cl-].[Al+3].[Cl-].[Cl-].[Na]>CO.C(OCC)(=O)C.ClCCl>[CH3:10][O:11][C:12](=[O:18])[CH2:13][CH2:14][C:15]([C:6]1[CH:7]=[CH:8][C:3]([CH2:2][CH2:1][OH:9])=[CH:4][CH:5]=1)=[O:16]

Participants

8

Reactant 4

HCID 60542-PhenylethanolHCID 73888Butanoic acid, 4-chloro-4-oxo-, methyl esterHCID 5360545SodiumHCID 6451240Aluminum(III) Chloride

Product 1

HCID 596786384-[4-(2-Hydroxyethyl)phenyl]-4-oxo-butyric acid methyl esterYield 57%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a dry 250 mL flask under a nitrogen atmosphere was added phenethyl alcohol (2.50 g, 0.02 mol), anhydrous dichloromethane (150 mL), and methyl-4-chloro-4-oxobutyrate (6.02 g, 0.04 mol). The contents of the flask were cooled to 0° C. with an ice bath. To the solution was added aluminum chloride (25 g, 0.2 mol) in portions being careful to avoid a violent exotherm. The resulting yellowish mixture was stirred for 3 hours. At this point the reaction was quenched with ice water. The mixture was diluted with dichloromethane and transferred to a separatory funnel. The organic layer was washed with a saturated solution of sodium bicarbonate, brine and then dried over magnesium sulfate. Filtration and concentration of the filtrate under reduced pressure provided a crude yellow oil. The oil was suspended in anhydrous methanol (100 mL) and sodium metal was added to the mixture until a pH of 9 was obtained. The mixture was stirred for 3 hours. The volume was reduced and then diluted with ethyl acetate. The solution was transferred to a separatory funnel and washed with aqueous 0.05 N hydrochloric acid, brine and dried over magnesium sulfate. The solution was concentrated under reduced pressure to give a crude yellow oil with a mass of 5.88 g. Column chromatography [silica gel; eluent hexanes-ethyl acetate (3:2)] provided the desired product (2.69 g, 57%). 1H(CDCl3) δ(ppm): 2.65 (t, 2H); 2.81 (t, 2H); 3.19 (t, 2H); 3.6 (s, 3H); 3.75 (t, 2H); 7.22 (d, 2H); 7.81 (d, 2H). 13C(CDCl3) δ(ppm): 27.76, 33.03, 38.66, 51.52, 62.68, 127.97, 128.99, 134.47, 144.78, 173.21, 197.64.

Workup

  1. customAt this point the reaction was quenched with ice water
  2. additionThe mixture was diluted with dichloromethane
  3. customtransferred to a separatory funnel
  4. washThe organic layer was washed with a saturated solution of sodium bicarbonate, brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationFiltration and concentration of the filtrate under reduced pressure
  7. customprovided a crude yellow oil
  8. customwas obtained
  9. stirringThe mixture was stirred for 3 hours
  10. customThe solution was transferred to a separatory funnel
  11. washwashed with aqueous 0.05 N hydrochloric acid, brine
  12. dry with materialdried over magnesium sulfate
  13. concentrationThe solution was concentrated under reduced pressure
  14. customto give a crude yellow oil with a mass of 5.88 g

Sources & evidence

ORD record
ord-e92fd7ac81ca43cbae5eb5d092667e99
Source dataset
uspto-grants-2015_10
Patent number
US09161997B2

Reaction notes

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