Triethylamine → tert-butyl 4-{3-[(3R)-3-{[1-(3-bromo-5-fluorophenyl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

HRID 526361Notes

Reaction equation

HRID 526361 reaction equation
[CH3:1][O:2][C:3](=[O:15])[CH2:4][CH:5]([NH2:14])[C:6]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]([Br:13])[CH:7]=1.O=C1CCC(=O)N1[O:23][C:24]([C@@H:26]1[CH2:31][CH2:30][CH2:29][N:28]([C:32](=[O:48])[CH2:33][CH2:34][CH:35]2[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH2:36]2)[CH2:27]1)=O.C(N(CC)CC)C.[Cl-].[NH4+]>CN(C)C=O.ClCCl>[Br:13][C:8]1[CH:7]=[C:6]([CH:5]([NH:14][C:24]([C@@H:26]2[CH2:31][CH2:30][CH2:29][N:28]([C:32](=[O:48])[CH2:33][CH2:34][CH:35]3[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:46])([CH3:45])[CH3:47])=[O:42])[CH2:37][CH2:36]3)[CH2:27]2)=[O:23])[CH2:4][C:3]([O:2][CH3:1])=[O:15])[CH:11]=[C:10]([F:12])[CH:9]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 712589093-Amino-3-(3-bromo-5-fluorophenyl)propionic acid methyl 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 71258942tert-butyl 4-{3-[(3R)-3-{[1-(3-bromo-5-fluorophenyl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylateYield 125%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

587.2 mg (2.13 mmol) 3-amino-3-(3-bromo-5-fluoro-phenyl)-propionic acid methyl ester were dissolved in 8.2 ml N,N-dimethylformamide and cooled to 0° C. To this solution was added a solution of 1100 mg (2.36 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 0.89 ml (6.38 mmol) triethylamine in 8.2 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 1.66 g (125%) tert-butyl 4-{3-[(3R)-3-{[1-(3-bromo-5-fluorophenyl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate with 80% purity.

Workup

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

Sources & evidence

ORD record
ord-f41e9e32f5fd4af5b244b406dfe38fb3
Source dataset
uspto-grants-2016_05
Patent number
US09345793B2

Reaction notes

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