Reaktion #4892

Reaktionsgleichung

N-methyl-3-pyrrolidinylmesylate

mesylate

2-chloro-5-nitrobenzamide

N-methyl-3-pyrrolidinylmesylate

sodium hydride

sodium hydride

→

crude crystals

Ausbeute 12.0%

2-(1-Methyl-3-pyrrolidinyloxy)-5-nitrobenzamide

Ausbeute 12.0%

Lösungsmittel

dimethylformamide

dimethylformamide

dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added
2. 2
   TemperaturThe reaction mixture was heated to 135° C. for 24 hr
3. 3
   workup.ADDITIONwas added
4. 4
   TemperaturHeating
5. 5
   workup.WAITwas continued for 24 hr
6. 6
   Temperaturafter cooling the reaction mixture to 100° C
7. 7
   TemperaturThe reaction mixture was maintained at 100° C. for 24 hr
8. 8
   SonstigeThe dimethylformamide was removed by rotary evaporation at 60° C.
9. 9
   Waschenwashed with 3×200 ml of 1N sodium hydroxide and 2×200 ml water
10. 10
    ExtraktionThe organic layer was extracted with 3×200 ml of 1N hydrochloric acid
11. 11
    Waschenwashed with ~200 ml chloroform
12. 12
    Extraktionextracted with 2×300 ml of methylene chloride
13. 13
    Trocknendried over sodium sulfate
14. 14
    Filtrationfiltered
15. 15
    Einengenconcentrated by rotary evaporation
16. 16
    SonstigeThe residue was crystallized from toluene

Vorschrift

To a cooled suspension of sodium hydride (2.42 g of 60% content 0.06 mole) in 50 ml of dimethylformamide under nitrogen was added dropwise a solution of 10 g (0.055 mole) of 2-chloro-5-nitrobenzamide in 20 ml dimethylformamide. The suspension was stirred at room temperature for 1 hr and heated to 60° C. at which time 9.9 g (0.055 mole) of N-methyl-3-pyrrolidinylmesylate (freshly prepared) in 10 ml of dimethylformamide was added. The reaction mixture was heated to 135° C. for 24 hr. Since little product was observed, 9.9 g (0.055 mole) addition N-methyl-3-pyrrolidinylmesylate and 1.21 g (60% in oil, 0.03 mole) of sodium hydride was added. Heating was continued for 24 hr. Another 4 equivalents of the above mesylate was added after cooling the reaction mixture to 100° C. The reaction mixture was maintained at 100° C. for 24 hr. The dimethylformamide was removed by rotary evaporation at 60° C., 0.5 mm Hg. The residue was taken up in 400 ml of methylene chloride and washed with 3×200 ml of 1N sodium hydroxide and 2×200 ml water. The organic layer was extracted with 3×200 ml of 1N hydrochloric acid. The aqueous extracts were combined and washed with ~200 ml chloroform. The aqueous layer was made basic with concentrated sodium hydroxide and extracted with 2×300 ml of methylene chloride. The organic extracts were combined, dried over sodium sulfate, filtered, and concentrated by rotary evaporation. The residue was crystallized from toluene to give 1.7 g (12%) of crude crystals. One recrystallization from toluene afforded light beige crystals, m.p. 215°-10° C.

Quelle