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Citric Acid → 2-[3(S)-(tert-butoxycarbonyl)amino-5(S)-(p-tert-butyl-benzyl)-2(S)-hydroxy-6-methyl-heptyl]-N-butyl-acrylamide

HRID 264883
ノート
印刷プレビュー

反応式

HRID 264883 の反応式
[CH2:1]([NH:5][C:6](=[O:10])[C:7]([CH3:9])=[CH2:8])[CH2:2][CH2:3][CH3:4].C([Li])CCC.C(O[C@@:21]([NH2:42])([C:24](=C=O)[C@H:25]([CH:37]([CH3:39])[CH3:38])[CH2:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]([CH3:36])([CH3:35])[CH3:34])=[CH:29][CH:28]=1)[CH:22]=[O:23])(C)(C)C.C(O)(=O)[CH2:44][C:45]([CH2:50]C(O)=O)([C:47](O)=O)[OH:46].[O:56]1CCC[CH2:57]1>CCCCCC.O1C=CC=C1.O1CCCC1.CC(C)[O-].CC(C)[O-].CC(C)[O-].Cl[Ti+3].C(OCC)C.O>[CH2:1]([NH:5][C:6](=[O:10])[C:7](=[CH2:9])[CH2:8][C@H:22]([OH:23])[C@@H:21]([NH:42][C:57]([O:46][C:45]([CH3:44])([CH3:47])[CH3:50])=[O:56])[CH2:24][C@@H:25]([CH:37]([CH3:39])[CH3:38])[CH2:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]([CH3:36])([CH3:35])[CH3:34])=[CH:29][CH:28]=1)[CH2:2][CH2:3][CH3:4]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

11

反応物 5

HCID 311Citric AcidHCID 8028TetrahydrofuranHCID 9855497N-ButylmethacrylamideHCID 866064382(S)tert-butoxy-carbonyl-amino-4(S)-isopropyl-5-(p-tert-butylphenyl)-pentanalHCID 178418339Butyllithium

生成物 1

HCID 54501741
2-[3(S)-(tert-butoxycarbonyl)amino-5(S)-(p-tert-butyl-benzyl)-2(S)-hydroxy-6-methyl-heptyl]-N-butyl-acrylamide

試薬・触媒・溶媒 5

HCID 11673339Chlorotitaniumtriisopropoxide触媒HCID 962Water溶媒HCID 3283Diethyl Ether溶媒HCID 8058Hexane溶媒2 回HCID 22709418Tetrahydrofuran furan溶媒

反応条件

温度
0 °C

実験手順

695 mg of methacrylic acid butylamide are dissolved in 30 ml of tetrahydrofuran and, at -75° C., 6.2 ml of 1.6M n-butyllithium in hexane are added thereto. The reaction mixture is stirred for 30 minutes at 0° C. and then, at -75° C., 9.8 ml of 1M chlorotitanium triisopropoxide in hexane are added thereto. The mixture is stirred for a further 15 minutes at -75° C. and then, at the same temperature, a solution of 924 mg of 2(S)-tert-butoxy-carbonyl-amino-4(S)-isopropyl-5-(p-tert-butyl-phenyl)-pentanal in 10 ml of tetrahydrofuran furan is added dropwise thereto. The reaction mixture is then stirred further for 15 minutes at -75° C. and for 70 minutes at 0° C. and then, in succession, 15 ml of 10% aqueous citric acid solution, water and diethyl ether are added thereto. The product is extracted repeatedly with diethyl ether. The diastereoisomeric mixture is separated by FC (700 g of silica gel, eluant: dichloromethane/diethyl ether=9:1). The title compound is obtained: diastereoisomer I: Rf (dichloromethane/diethyl ether=9:1)=0.21; diastereoisomer II: Rf (dichloromethane/diethyl ether=9:1)=0.14.

後処理

  1. stirringThe mixture is stirred for a further 15 minutes at -75° C.
  2. stirringThe reaction mixture is then stirred further for 15 minutes at -75° C. and for 70 minutes at 0° C.
  3. extractionThe product is extracted repeatedly with diethyl ether
  4. customThe diastereoisomeric mixture is separated by FC (700 g of silica gel, eluant: dichloromethane/diethyl ether=9:1)

出典と根拠

ORDレコード
ord-347d9206030446e2bb11e6aab03f236c
出典データセット
uspto-grants-1997_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US05646143

反応ノート

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