تفاعل #4892

معادلة التفاعل

N-methyl-3-pyrrolidinylmesylate

mesylate

2-chloro-5-nitrobenzamide

N-methyl-3-pyrrolidinylmesylate

sodium hydride

sodium hydride

→

crude crystals

المردود 12.0%

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

المردود 12.0%

المذيبات

dimethylformamide

dimethylformamide

dimethylformamide

ظروف التفاعل

المعالجة

1. 1
   workup.ADDITIONwas added
2. 2
   درجة الحرارةThe reaction mixture was heated to 135° C. for 24 hr
3. 3
   workup.ADDITIONwas added
4. 4
   درجة الحرارةHeating
5. 5
   workup.WAITwas continued for 24 hr
6. 6
   درجة الحرارةafter cooling the reaction mixture to 100° C
7. 7
   درجة الحرارةThe reaction mixture was maintained at 100° C. for 24 hr
8. 8
   أخرىThe dimethylformamide was removed by rotary evaporation at 60° C.
9. 9
   غسيلwashed with 3×200 ml of 1N sodium hydroxide and 2×200 ml water
10. 10
    استخلاصThe organic layer was extracted with 3×200 ml of 1N hydrochloric acid
11. 11
    غسيلwashed with ~200 ml chloroform
12. 12
    استخلاصextracted with 2×300 ml of methylene chloride
13. 13
    تجفيفdried over sodium sulfate
14. 14
    ترشيحfiltered
15. 15
    تركيزconcentrated by rotary evaporation
16. 16
    أخرىThe residue was crystallized from toluene

الإجراء التجريبي

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.

المصدر