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

HRID 464434

反応式

HRID 464434 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([CH:14]=[C:15]([Cl:17])[CH:16]=1)[O:5][CH:6]1[CH2:10][CH2:9][N:8]([C:11](Cl)=[O:12])[CH2:7]1.[CH2:18]([N:20]([CH2:26][CH3:27])[CH2:21][CH2:22][NH:23][CH2:24][CH3:25])[CH3:19].C(O)(=O)C(O)=O>O1CCCC1.CC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:14]=[C:15]([Cl:17])[CH:16]=1)[O:5][CH:6]1[CH2:10][CH2:9][N:8]([C:11]([N:23]([CH2:22][CH2:21][N:20]([CH2:26][CH3:27])[CH2:18][CH3:19])[CH2:24][CH3:25])=[O:12])[CH2:7]1

参加物

6

反応物 3

HCID 971Oxalic AcidHCID 66040TriethylethylenediamineHCID 135342583-(3,5-Dichlorophenoxy)-1-pyrrolidinecarbonyl Chloride

生成物 1

HCID 202630403-(3,5-Dichlorophenoxy)-N-[2-(diethylamino)ethyl]-N-ethyl-1-pyrrolidinecarboxamide収率 78.7%

試薬・触媒・溶媒 2

HCID 180Acetone溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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.

後処理

  1. filtrationThe mixture filtered
  2. customto remove a small amount of precipitate
  3. additionThe filtrate was diluted with 200 ml of ice water
  4. extractionextracted with 3×100 ml of benzene
  5. washthe combined extracts washed with water
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customto give a pale brown oil, 8.24 g
  9. temperatureheated
  10. dissolutionuntil dissolved
  11. customA fine amorphous gel was removed by filtration
  12. additionthe filtrate diluted with isopropyl ether until cloudy
  13. customto precipitate overnight
  14. customAfter 2 weeks the oil which separated from the acetone/isopropyl ether
  15. customto crystallize
  16. customThe solvents were removed by decantation
  17. additionThe free base in methylene chloride was treated with 200 g of florisil
  18. additiondiluted with enough methylene chloride
  19. customto give a stirrable slurry
  20. filtrationAfter 30 minutes the slurry was filtered
  21. washthe florisil washed with 2 volumes of methylene chloride
  22. washThe column was washed with an additional 500 ml of methanol
  23. concentrationConcentration in vacuo of the combined methanol effluents

出典と根拠

ORDレコード
ord-3e1878949f9a41fa8a26303ab7d07ff1
出典データセット
uspto-grants-1985_10
特許番号
US04547514

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