Triethylamine → 4-(3-{(R)-3-[(S)-2-tert-butoxycarbonyl-1-(4-hydroxy-phenyl)-ethylcarbamoyl]-piperidin-1-yl}-3-oxo-propyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 526369ノート

反応式

HRID 526369 の反応式
[C:1]([O:5][C:6](=[O:17])[CH2:7][C@H:8]([NH2:16])[C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].O=C1CCC(=O)N1[O:25][C:26]([C@@H:28]1[CH2:33][CH2:32][CH2:31][N:30]([C:34](=[O:50])[CH2:35][CH2:36][CH:37]2[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][CH2:38]2)[CH2:29]1)=O.C(N(CC)CC)C.[Cl-].[NH4+]>CN(C)C=O.ClCCl>[C:46]([O:45][C:43]([N:40]1[CH2:39][CH2:38][CH:37]([CH2:36][CH2:35][C:34]([N:30]2[CH2:31][CH2:32][CH2:33][C@@H:28]([C:26](=[O:25])[NH:16][C@H:8]([C:9]3[CH:10]=[CH:11][C:12]([OH:15])=[CH:13][CH:14]=3)[CH2:7][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:17])[CH2:29]2)=[O:50])[CH2:42][CH2:41]1)=[O:44])([CH3:49])([CH3:48])[CH3:47]

参加物

7

反応物 4

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 71259013(S)-3-amino-3-(4-hydroxy-phenyl)-propionic acid tert-butyl esterHCID 89407588tert-butyl 4-{3-[(3R)-3-{[(2,5-dioxopyrrolidin-1-yl)oxy]carbonyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

生成物 1

HCID 712589314-(3-{(R)-3-[(S)-2-tert-butoxycarbonyl-1-(4-hydroxy-phenyl)-ethylcarbamoyl]-piperidin-1-yl}-3-oxo-propyl)-piperidine-1-carboxylic acid tert-butyl ester収率 102%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

214.0 mg (0.90 mmol) (S)-3-amino-3-(4-hydroxy-phenyl)-propionic acid tert-butyl ester were dissolved in 3.5 ml N,N-dimethylformamide and cooled to 0° C. To this solution was added a solution of 466.4 mg (1.00 mmol) tert-butyl 4-{3-[(3R)-3-{[(2,5-dioxopyrrolidin-1-yl)oxy]carbonyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate (example 5c) and 0.38 ml (2.71 mmol) triethylamine in 3.5 ml dichloromethane. The mixture was kept at 6° C. for 20 hours. Saturated ammonium chloride solution was added and the mixture extracted with dichloromethane. The organic layer was dried over sodium sulfate and concentrated in vacuum to give 820 mg. Chromatography over 5 g silica gel (dichloromethane/ethanol 100/0-95/5-90/10) gave 539 mg (102%) 4-(3-{(R)-3-[(S)-2-tert-butoxycarbonyl-1-(4-hydroxy-phenyl)-ethylcarbamoyl]-piperidin-1-yl}-3-oxo-propyl)-piperidine-1-carboxylic acid tert-butyl ester

後処理

  1. extractionthe mixture extracted with dichloromethane
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated in vacuum
  4. customto give 820 mg

出典と根拠

ORDレコード
ord-93933cc0bdc8471b8bacc3e132f08c45
出典データセット
uspto-grants-2016_05
特許番号
US09345793B2

反応ノート

読み込み中…