Ethylmorpholine → N-benzyloxycarbonyl-L-alanyl-L-proline ethylamide

HRID 47042ノート

反応式

HRID 47042 の反応式
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:14]([N:16]1[CH2:23][CH2:22][CH2:21][C@H:17]1[C:18]([OH:20])=O)=[O:15])[CH3:13])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:24]([N:26]1CCOCC1)[CH3:25].ClC(OCC(C)C)=O.[Cl-].C([NH3+])C>O1CCCC1.CN(C)C=O>[CH2:24]([NH:26][C:18](=[O:20])[C@@H:17]1[CH2:21][CH2:22][CH2:23][N:16]1[C:14](=[O:15])[C@H:12]([CH3:13])[NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10])[CH3:25]

参加物

7

反応物 4

HCID 7525Ethylmorpholine2 回HCID 62365Isobutyl chloroformateHCID 5388928Z-Ala ProlinalHCID 132503489Ethylamine hydrochloride

生成物 1

HCID 13749998N-benzyloxycarbonyl-L-alanyl-L-proline ethylamide収率 68%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-10 °C

実験手順

32 g (0.1 mol) of N-benzyloxycarbonyl-L-alanyl-L-proline were dissolved in 250 ml of dry tetrahydrofuran and the solution was cooled to -10° C. 12.7 ml (0.1 mol) of N-ethylmorpholine and 13.1 ml (0.1 mol) of isobutyl chloroformate were then added and the solution was stirred at -10° C. for 20 minutes. To this mixture was then added a further 12.7 ml of N-ethylmorpholine followed by a solution of 8.15 g (0.1 mol) of ethylammonium chloride in 50 ml of dimethylformamide. The solution was stirred for 1 hour at 0° C. then left for 16 hours at room temperature. The solvents were removed by evaporation and the residue was triturated with 450 ml of ethyl acetate and washed successively with 200 ml of 1-N hydrochloric acid, 200 ml of water and 200 ml of 5% sodium bicarbonate solution. After drying over sodium sulphate and filtration, the solvent was removed by evaporation. The resulting oil crystallised slowly from ethyl acetate ether to yield 20.7 g of N-benzyloxycarbonyl-L-alanyl-L-proline ethylamide of melting point 110°-113° C. Evaporation of the mother liquors followed by treatment with ethyl acetate/ether gave a further crop of 1.2 g of melting point 107°-110° C.; total yield 68% [α]D20 =-96.0° (c=1.04% in methanol).

後処理

  1. stirringThe solution was stirred for 1 hour at 0° C.
  2. waitthen left for 16 hours at room temperature
  3. customThe solvents were removed by evaporation
  4. customthe residue was triturated with 450 ml of ethyl acetate
  5. washwashed successively with 200 ml of 1-N hydrochloric acid, 200 ml of water and 200 ml of 5% sodium bicarbonate solution
  6. dry with materialAfter drying over sodium sulphate and filtration
  7. customthe solvent was removed by evaporation
  8. customThe resulting oil crystallised slowly from ethyl acetate ether

出典と根拠

ORDレコード
ord-920d7064853a4581bc6800d4f7d59197
出典データセット
uspto-grants-1979_11
特許番号
US04176116

反応ノート

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