Potassium Iodide → 3-Methoxy-4-[3-(1-pyrrolidinyl)propoxy]-benzoic acid Hydrochloride

HRID 22778

Reaktionsgleichung

Reaktionsgleichung von HRID 22778
[OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[O:11][CH3:12].[N:13]1([CH2:18][CH2:19][CH2:20][Cl:21])[CH2:17][CH2:16][CH2:15][CH2:14]1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CN(C=O)C>[ClH:21].[CH3:12][O:11][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:2]=1[O:1][CH2:20][CH2:19][CH2:18][N:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1)[C:6]([OH:8])=[O:7]

Komponenten

6

Edukt 4

HCID 4875Potassium IodideHCID 8468Vanillic AcidHCID 11430Potassium CarbonateHCID 113210281-(3-Chloropropyl)-pyrrolidine

Produkt 1

HCID 248202363-Methoxy-4-[3-(1-pyrrolidinyl)propoxy]-benzoic acid HydrochlorideAusbeute 77,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of 4-hydroxy-3-methoxybenzoic acid (8.4 g), 3-(pyrrolidin-1-yl)propyl chloride (J. Amer. Chem. Soc., 1955, 77, 2272; 14.75 g), potassium carbonate (13.8 g), potassium iodide (1.66 g) and DMF (150 ml) was stirred and heated to 100° C. for 3 hours. The mixture was allowed to cool to ambient temperature, filtered and the filtrate was evaporated. The residue was dissolved in ethanol (75 ml), 2N aqueous sodium hydroxide solution (75 ml) was added and the mixture was heated to 90° C. for 2 hours. The mixture was concentrated by evaporation and acidified by the addition of concentrated aqueous hydrochloric acid. The resultant mixture was washed with diethyl ether and then purified by column chromatography using a Diaion (trade mark of Mitsubishi) HP20SS resin column, eluting with water and then with a gradient of methanol (0 to 25%) in dilute hydrochloric acid (pH2.2). The methanol was removed by evaporation and the aqueous residue was freeze dried to give 3-methoxy-4-(3-pyrrolidin-1-ylpropoxy)benzoic acid hydrochloride (12.2 g); NMR Spectrum: (DMSOd6 and CF3CO2D) 2.2 (m, 2H), 3.15 (t, 2H), 3.3 (t, 2H), 3.5 (d, 2H), 3.7 (t, 2H), 3.82 (s, 3H), 4.05 (d, 2H), 4.15 (t, 2H), 7.07 (d, 1H), 7.48 (s, 1H), 7.59 (d, 1H).

Aufarbeitung

  1. temperatureto cool to ambient temperature
  2. filtrationfiltered
  3. customthe filtrate was evaporated
  4. dissolutionThe residue was dissolved in ethanol (75 ml)
  5. addition2N aqueous sodium hydroxide solution (75 ml) was added
  6. temperaturethe mixture was heated to 90° C. for 2 hours
  7. concentrationThe mixture was concentrated by evaporation
  8. additionacidified by the addition of concentrated aqueous hydrochloric acid
  9. washThe resultant mixture was washed with diethyl ether
  10. custompurified by column chromatography
  11. washeluting with water
  12. customThe methanol was removed by evaporation
  13. customdried

Quellen und Nachweise

ORD-Eintrag
ord-5943373448604eeba3420d46c4eb1099
Quelldatensatz
uspto-grants-2005_02
Patentnummer
US06849625B2

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