1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (R)-3-(4-{[tert-Butoxycarbonyl-(4-cyclohexylphenyl)amino]methyl}benzoylamino)-2-hydroxy-propionic acid methyl ester

HRID 412458ノート

反応式

HRID 412458 の反応式
[C:1]([O:5][C:6]([N:8]([CH2:21][C:22]1[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][CH:23]=1)[C:9]1[CH:14]=[CH:13][C:12]([CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]2)=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[CH3:52][O:53][C:54](=[O:59])[C@H:55]([OH:58])[CH2:56][NH2:57]>CN(C=O)C.C(N(C(C)C)CC)(C)C.O>[CH3:52][O:53][C:54](=[O:59])[C@H:55]([OH:58])[CH2:56][NH:57][C:26](=[O:27])[C:25]1[CH:29]=[CH:30][C:22]([CH2:21][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C:9]2[CH:10]=[CH:11][C:12]([CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]3)=[CH:13][CH:14]=2)=[CH:23][CH:24]=1

参加物

8

反応物 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 11665404methyl (2R)-3-amino-2-hydroxypropanoateHCID 223111164-{[tert-Butoxycarbonyl-(4-cyclohexylphenyl)amino]methyl}benzoic acid

生成物 1

HCID 69733520(R)-3-(4-{[tert-Butoxycarbonyl-(4-cyclohexylphenyl)amino]methyl}benzoylamino)-2-hydroxy-propionic acid methyl ester

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒2 回HCID 81531Diisopropylethylamine溶媒

実験手順

4-{[tert-Butoxycarbonyl-(4-cyclohexylphenyl)amino]methyl}benzoic acid was dissolved in DMF (10 mL) and HOBt (0.40 g, 2.93 mmol) and EDAC (0.52 g, 2.73 mmol) were added. The reaction mixture was stirred for 45 min. Then a solution of (R)-3-amino-2-hydroxypropionic acid methyl ester in DMF (8 mL) and diisopropylethylamine (0.46 mL) were added. The mixture was stirred overnight. The reaction mixture was diluted with water (40 mL) and extracted with ethyl acetate (75 mL). The aqueous phase was extracted with ethyl acetate (30 mL). The combined organic phases were washed with hydrochloric acid (0.2 N, 3×30 mL), water: saturated sodium chloride (3×30 mL), dried with magnesium sulphate and concentrated in vacua. The residue was purified by column chromatography on silica gel (100 g) using mixtures of ethyl acetate and n-heptane (1 L (1:1) and 0.5 L (7:3)) as eluents to afford 0.77 g (R)-3-(4-{[tert-butoxycarbonyl-(4-cyclohexylphenyl)amino]methyl}benzoylamino)-2-hydroxypropionic acid methyl ester.

後処理

  1. stirringThe mixture was stirred overnight
  2. extractionextracted with ethyl acetate (75 mL)
  3. extractionThe aqueous phase was extracted with ethyl acetate (30 mL)
  4. washThe combined organic phases were washed with hydrochloric acid (0.2 N, 3×30 mL), water
  5. dry with materialsaturated sodium chloride (3×30 mL), dried with magnesium sulphate
  6. concentrationconcentrated in vacua
  7. customThe residue was purified by column chromatography on silica gel (100 g)

出典と根拠

ORDレコード
ord-0ded09a6921449428dca448752461c6d
出典データセット
uspto-grants-2003_05
特許番号
US06562807B2

反応ノート

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