Reaktion #51056

Reaktionsgleichung

4-hydroxy-3-methoxybenzoic acid

3-(pyrrolidin-1-yl)propyl chloride

potassium carbonate

potassium iodide

→

3-methoxy-4-(3-pyrrolidin-1-ylpropoxy)benzoic acid hydrochloride

Ausbeute 77.3%

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturto cool to ambient temperature
2. 2
   Filtrationfiltered
3. 3
   Sonstigethe filtrate was evaporated
4. 4
   workup.DISSOLUTIONThe residue was dissolved in ethanol (75 ml)
5. 5
   workup.ADDITION2N aqueous sodium hydroxide solution (75 ml) was added
6. 6
   Temperaturthe mixture was heated to 90° C. for 2 hours
7. 7
   EinengenThe mixture was concentrated by evaporation
8. 8
   workup.ADDITIONacidified by the addition of concentrated aqueous hydrochloric acid
9. 9
   WaschenThe resultant mixture was washed with diethyl ether
10. 10
    Sonstigepurified by column chromatography
11. 11
    Wascheneluting with water
12. 12
    SonstigeThe methanol was removed by evaporation
13. 13
    Sonstigedried

Vorschrift

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).

Quelle