1-Hydroxybenzotriazole → (2S)-2-{(1R,2S)-2-[2-(3-hydroxy-phenyl)-ethylcarbamoyl]-1-methylsulfanyl-propyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1582735ノート

反応式

HRID 1582735 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C@H:13]([S:19][CH3:20])[C@H:14]([C:16]([OH:18])=O)[CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].Br.[OH:22][C:23]1[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=1)[CH2:26][CH2:27][NH2:28].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C@H:13]([S:19][CH3:20])[C@H:14]([C:16](=[O:18])[NH:28][CH2:27][CH2:26][C:25]1[CH:29]=[CH:30][CH:31]=[C:23]([OH:22])[CH:24]=1)[CH3:15])=[O:7])([CH3:2])([CH3:3])[CH3:4]

参加物

7

反応物 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 11522334(2S)-2-[(R,2S)-2-carboxy-1-methylsulfanyl-propyl]-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 227178563-(2-Aminoethyl)phenol hydrobromide

生成物 1

HCID 69551291(2S)-2-{(1R,2S)-2-[2-(3-hydroxy-phenyl)-ethylcarbamoyl]-1-methylsulfanyl-propyl]-pyrrolidine-1-carboxylic acid tert-butyl ester収率 87.5%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a stirred solution of (2S)-2-[(1R,2S)-2-carboxy-1-methylsulfanyl-propyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (1.7 g, 5.6 mmol) in CH2Cl2 (20 mL) were added 3-hydroxyphenethylamine hydrobromide (2.44 g, 11.2 mmol), BOP(3.72 g, 8.4 mmol), HOBT (1.29 g, 8.4 mmol), and diisopropylethylamine (4.88 mL, 28.0 mmol) at room temperature. After being stirred at room temperature for 2 hr, the mixture was quenched with 1N HCl (80 mL×3), extracted with AcOEt, dried (MgSO4) and concentrated in vacuo to give a crude oil, which was purified by flash column chromatography (hexane:AcOEt=1:1) to give (2S)-2-{(1R,2S)-2-[2-(3-hydroxy-phenyl)-ethylcarbamoyl]-1-methylsulfanyl-propyl}-pyrrolidine-1-carboxylic acid tert-butyl ester as a gum (2.07 g, 87%).

後処理

  1. customthe mixture was quenched with 1N HCl (80 mL×3)
  2. extractionextracted with AcOEt
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customto give a crude oil, which
  6. customwas purified by flash column chromatography (hexane:AcOEt=1:1)

出典と根拠

ORDレコード
ord-843db06507cd4bf590471b7a274ebb05
出典データセット
uspto-grants-2004_05
特許番号
US06737409B2

反応ノート

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