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 526369노트

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HRID 526369 반응식
[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]

참가 물질

7

반응물 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

생성물 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 ester수율 102%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

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온도
0 °C

실험 절차

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

후처리

  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

출처 및 근거

ORD 기록
ord-93933cc0bdc8471b8bacc3e132f08c45
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09345793B2

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