반응 #323320

반응 방정식

N-methyl-3-pyrrolidinylmesylate

mesylate

2-chloro-5-nitrobenzamide

N-methyl-3-pyrrolidinylmesylate

sodium hydride

sodium hydride

→

crude crystals

수율 12.0%

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

수율 12.0%

용매

dimethylformamide

dimethylformamide

dimethylformamide

반응 조건

후처리

1. 1
   workup.ADDITIONwas added
2. 2
   온도The reaction mixture was heated to 135° C. for 24 hr
3. 3
   온도Heating
4. 4
   workup.WAITwas continued for 24 hr
5. 5
   온도after cooling the reaction mixture to 100° C
6. 6
   온도The reaction mixture was maintained at 100° C. for 24 hr
7. 7
   기타The dimethylformamide was removed by rotary evaporation at 60° C.
8. 8
   세척washed with 3×200 ml of 1N sodium hydroxide and 2×200 ml water
9. 9
   추출The organic layer was extracted with 3×200 ml of 1N hydrochloric acid
10. 10
    세척washed with ~200 ml chloroform
11. 11
    추출extracted with 2×300 ml of methylene chloride
12. 12
    건조dried over sodium sulfate
13. 13
    여과filtered
14. 14
    농축concentrated by rotary evaporation
15. 15
    기타The residue was crystallized from toluene

실험 절차

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) additional 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.

출처