4-Methylmorpholine → N-benzyloxycarbonyl-3-(1-naphthyl)-L-alanyl-L-leucine ethyl ester

HRID 255620ノート

反応式

HRID 255620 の反応式
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:24]([OH:26])=O)[CH2:13][C:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=[CH:16][CH:15]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1CCOCC1.C(Cl)(=O)OCC.Cl.[CH2:41]([O:43][C:44](=[O:51])[C@H:45]([CH2:47][CH:48]([CH3:50])[CH3:49])[NH2:46])[CH3:42]>O1CCCC1>[CH2:41]([O:43][C:44](=[O:51])[C@H:45]([CH2:47][CH:48]([CH3:50])[CH3:49])[NH:46][C:24](=[O:26])[C@H:12]([CH2:13][C:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=[CH:16][CH:15]=1)[NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10])[CH3:42]

参加物

6

反応物 4

HCID 79724-Methylmorpholine2 回HCID 10928Ethyl chloroformateHCID 7020250Z-1-Nal-OHHCID 11658447L-Leucine, ethyl ester, hydrochloride (1:1)

生成物 1

HCID 53922528N-benzyloxycarbonyl-3-(1-naphthyl)-L-alanyl-L-leucine ethyl ester

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-5 °C

実験手順

3.49 g (10 mmole) of N-benzyloxycarbonyl-3-(1-naphthyl)-L-alanine and 1.21 g (12 mmole) of N-methylmorpholine were dissolved in 30 ml of anhydrous tetrahydrofuran, and then, whilst cooling the solution at -5° C., 1.30 g (12 mmole) of ethyl chlorocarbonate was added dropwise, with stirring, over a period of 15 minutes. 2.35 g (12 mmole) of L-leucine ethyl ester hydrochloride [which had been suspended in 10 ml of methylene chloride and neutralized with 1.21 g (12 mmole) of N-methylmorpholine] were added. The mixture was stirred for 2 hours with ice cooling, and then left standing overnight at room temperature. It was then condensed by evaporation under reduced pressure. Water was added to the residue, and the precipitating oily substance was extracted with ethyl acetate. The organic extract was washed with 1N hydrochloric acid, water, a 5% w/v aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, in that order, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The N-benzyloxycarbonyl-3-(1-naphthyl)-L-alanyl-L-leucine ethyl ester thus obtained in a syrupy form was dissolved in 30 ml of dimethylformamide, and 5.06 g (100 mmole) of hydrazine hydrate were added to the solution. The mixture was stirred for 36 hours at room temperature. The reaction product was then condensed by evaporation under reduced pressure, and water was added to the residue. The colorless crystals produced were collected by filtration, thoroughly washed with water and dried in a desiccator to yield 4.23 g of the title compound melting at 200°-204° C.

後処理

  1. stirringThe mixture was stirred for 2 hours with ice cooling
  2. waitleft
  3. waitstanding overnight at room temperature
  4. customcondensed
  5. customby evaporation under reduced pressure
  6. additionWater was added to the residue
  7. extractionthe precipitating oily substance was extracted with ethyl acetate
  8. extractionThe organic extract
  9. washwas washed with 1N hydrochloric acid, water
  10. dry with materiala 5% w/v aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, in that order, and then dried over anhydrous sodium sulfate
  11. distillationThe solvent was distilled off under reduced pressure

出典と根拠

ORDレコード
ord-9fabaaa79a784741be2f10113e495655
出典データセット
uspto-grants-1987_10
特許番号
US04698329

反応ノート

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