1-Hydroxybenzotriazole → (2s)-2-((1r,2s)-2-{[2-(3-Hydroxy-phenyl)-ethyl]-methyl-carbamoyl}-1-methylsulfanyl-propyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1582736노트

반응식

HRID 1582736 반응식
[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.[CH3:22][NH:23][CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([OH:32])[CH:27]=1.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])[N:23]([CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([OH:32])[CH:27]=1)[CH3:22])[CH3:15])=[O:7])([CH3:2])([CH3:3])[CH3:4]

참가 물질

7

반응물 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 227178343-(2-(Methylamino)ethyl)phenol hydrobromide

생성물 1

HCID 58671475(2s)-2-((1r,2s)-2-{[2-(3-Hydroxy-phenyl)-ethyl]-methyl-carbamoyl}-1-methylsulfanyl-propyl)-pyrrolidine-1-carboxylic acid tert-butyl ester수율 56.4%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a stirred solution of (2S)-2-[(1R,2S)-2-carboxy-1-methylsulfanyl-propyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (1.70 g, 5.6 mmol) in CH2Cl2 (20 mL) were added N-methyl-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 (3.83 g), which was then purified by flash column chromatography (hexane:AcOEt=1:1) to give (2S)-2-((1R,2S)-2-{[2-(3-hydroxy-phenyl)-ethyl]-methyl-carbamoyl}-1-methylsulfanyl-propyl)-pyrrolidine-1-carboxylic acid tert-butyl ester as a gum (1.38 g, 56%).

후처리

  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 (3.83 g), which
  6. customwas then purified by flash column chromatography (hexane:AcOEt=1:1)

출처 및 근거

ORD 기록
ord-0f59efc7d85f4979bb7cff607902c26e
출처 데이터셋
uspto-grants-2004_05
특허 번호
US06737409B2

반응 노트

불러오는 중…