Hydrochloric Acid → Methyl 3-(4-{[4-(methyloxy)phenyl]carbonyl}phenyl)propanoate

HRID 229242Notes

Reaction equation

HRID 229242 reaction equation
[CH3:1][O:2][C:3](=[O:15])[CH2:4][CH2:5][C:6]1[CH:14]=[CH:13][C:9]([C:10]([OH:12])=O)=[CH:8][CH:7]=1.C(Cl)(=O)C(Cl)=O.[C:22]1([O:28][CH3:29])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[Al+3].[Cl-].[Cl-].[Cl-].Cl>C(Cl)Cl.CN(C=O)C>[CH3:29][O:28][C:22]1[CH:27]=[CH:26][C:25]([C:10]([C:9]2[CH:8]=[CH:7][C:6]([CH2:5][CH2:4][C:3]([O:2][CH3:1])=[O:15])=[CH:14][CH:13]=2)=[O:12])=[CH:24][CH:23]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 7519AnisoleHCID 65578Oxalyl chlorideHCID 6451240Aluminum(III) ChlorideHCID 113102944-(3-Methoxy-3-oxopropyl)benzoic acid

Product 1

HCID 68654356Methyl 3-(4-{[4-(methyloxy)phenyl]carbonyl}phenyl)propanoateYield 63%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

4-[3-(Methyloxy)-3-oxopropyl]benzoic acid (166) (1.0 g, 4.80 mmol) was dissolved in CH2Cl2 (25 mL). Oxalyl chloride (0.86 mL, 9.61 mmol) was added dropwise, followed by addition of two drops of DMF. The reaction mixture was stirred at room temperature for 2 h. Methylene chloride and the excess of oxalyl chloride were removed under vacuum. The residue was dissolved in CH2Cl2 (15 mL) with anisole (1.05 mL, 9.60 mmol). Cooled in an ice bath, AlCl3 (0.97 g, 7.20 mmol) was added in portions. The mixture was stirred at 0° C. for 3.5 h, then stirred at room temperature for 1.5 h. Poured into 1 N HCl (25 mL) with ice, the mixture was extracted with CH2Cl2 (3×50 mL). The combined CH2Cl2 extract was washed with saturated aqueous NaHCO3, brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give brown oil. The crude product was purified by chromatography on a silica gel column eluted with hexanes:EtOAc (8:1 to 5:1) to give 0.90 g (63%) of the title compound 167 as cotton-like white solid. 1H NMR (400 MHz, CDCl3): δ 2.68 (t, J=7.7 Hz, 2H), 3.03 (t, J=7.7 Hz, 2H), 3.68 (s, 3H), 3.89 (s, 3H), 6.96 (d, J=8.8 Hz, 2H), 7.30 (d, J=8.1 Hz, 2H), 7.70 (d, J=8.1 Hz, 2H), 7.81 (d, J=8.8 Hz, 2H). LCMS (ESI): m/z 299 (M+H)+.

Workup

  1. customMethylene chloride and the excess of oxalyl chloride were removed under vacuum
  2. temperatureCooled in an ice bath
  3. stirringThe mixture was stirred at 0° C. for 3.5 h
  4. stirringstirred at room temperature for 1.5 h
  5. extractionthe mixture was extracted with CH2Cl2 (3×50 mL)
  6. extractionThe combined CH2Cl2 extract
  7. washwas washed with saturated aqueous NaHCO3, brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated
  11. customto give brown oil
  12. customThe crude product was purified by chromatography on a silica gel column
  13. washeluted with hexanes:EtOAc (8:1 to 5:1)

Sources & evidence

ORD record
ord-ed37f7c3e25f490ca363702cf56558d9
Source dataset
uspto-grants-2009_07
Patent number
US07560589B2

Reaction notes

Loading…