반응 #551616

반응 방정식

oxalic acid

3-(3,5-dichlorophenoxy)-1-pyrrolidinecarbonyl chloride

N,N,N'-triethylethylenediamine

→

dark oil

수율 78.7%

3-(3,5-Dichlorophenoxy)-N-[2-(diethylamino)ethyl]-N-ethyl-1-pyrrolidinecarboxamide

수율 78.7%

용매

acetone

tetrahydrofuran

반응 조건

후처리

1. 1
   여과The mixture filtered
2. 2
   기타to remove a small amount of precipitate
3. 3
   workup.ADDITIONThe filtrate was diluted with 200 ml of ice water
4. 4
   추출extracted with 3×100 ml of benzene
5. 5
   세척the combined extracts washed with water
6. 6
   건조dried over magnesium sulfate
7. 7
   농축concentrated in vacuo
8. 8
   기타to give a pale brown oil, 8.24 g
9. 9
   온도heated
10. 10
    workup.DISSOLUTIONuntil dissolved
11. 11
    기타A fine amorphous gel was removed by filtration
12. 12
    workup.ADDITIONthe filtrate diluted with isopropyl ether until cloudy
13. 13
    기타to precipitate overnight
14. 14
    기타After 2 weeks the oil which separated from the acetone/isopropyl ether
15. 15
    기타to crystallize
16. 16
    기타The solvents were removed by decantation
17. 17
    workup.ADDITIONThe free base in methylene chloride was treated with 200 g of florisil
18. 18
    workup.ADDITIONdiluted with enough methylene chloride
19. 19
    기타to give a stirrable slurry
20. 20
    여과After 30 minutes the slurry was filtered
21. 21
    세척the florisil washed with 2 volumes of methylene chloride
22. 22
    세척The column was washed with an additional 500 ml of methanol
23. 23
    농축Concentration in vacuo of the combined methanol effluents

실험 절차

A stirred solution of 7 g (0.024 mole) of 3-(3,5-dichlorophenoxy)-1-pyrrolidinecarbonyl chloride in 70 ml of tetrahydrofuran was treated with 7 g (0.05 mole) of N,N,N'-triethylethylenediamine (slight exothermic) and stirred at ambient temperature overnight. The mixture filtered to remove a small amount of precipitate. The filtrate was diluted with 200 ml of ice water, extracted with 3×100 ml of benzene and the combined extracts washed with water, dried over magnesium sulfate and concentrated in vacuo to give a pale brown oil, 8.24 g. The oil was dissolved in acetone, treated with 1.9 g of oxalic acid and heated until dissolved. A fine amorphous gel was removed by filtration and the filtrate diluted with isopropyl ether until cloudy. The salt was allowed to precipitate overnight. After 2 weeks the oil which separated from the acetone/isopropyl ether failed to crystallize. The solvents were removed by decantation and the residual oil converted back to the free base. The free base in methylene chloride was treated with 200 g of florisil and diluted with enough methylene chloride to give a stirrable slurry. After 30 minutes the slurry was filtered and the florisil washed with 2 volumes of methylene chloride. The florisil was suspended in 500 ml of methanol and transferred to a column. The column was washed with an additional 500 ml of methanol. Concentration in vacuo of the combined methanol effluents gave 7.6 g of dark oil which was chromatographed on a 100 g alumina column by eluting with a 0-5% methanol/acetonitrile gradient. The first 2 fractions were discarded and the remainder combined and concentrated to an oil (5.2 g). The oil was dissolved in ethyl ether, filtered to remove traces of alumina, concentrated in vacuo and excess solvent removed by pumping under high vacuum at 55° C. for 18 hours.

출처