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 526369Notes

Reaction equation

HRID 526369 reaction equation
[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]

Participants

7

Reactant 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

Product 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 esterYield 102%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

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

Workup

  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

Sources & evidence

ORD record
ord-93933cc0bdc8471b8bacc3e132f08c45
Source dataset
uspto-grants-2016_05
Patent number
US09345793B2

Reaction notes

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