Dimethylformamide → (S)-2-[4-(3-tert-butoxycarbonylaminopropoxy)-2,6-dichlorobenzoylamino]-3-[4-(2,6-dichlorobenzoylamino)phenyl]propionic acid methyl ester

HRID 63726

Reaction equation

HRID 63726 reaction equation
[CH3:1][O:2][C:3](=[O:35])[C@@H:4]([NH:23][C:24](=[O:34])[C:25]1[C:30]([Cl:31])=[CH:29][C:28]([OH:32])=[CH:27][C:26]=1[Cl:33])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13](=[O:22])[C:14]2[C:19]([Cl:20])=[CH:18][CH:17]=[CH:16][C:15]=2[Cl:21])=[CH:8][CH:7]=1.[C:36]([O:40][C:41]([NH:43][CH2:44][CH2:45][CH2:46]Br)=[O:42])([CH3:39])([CH3:38])[CH3:37].C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O.CC(C)=O>[CH3:1][O:2][C:3](=[O:35])[C@@H:4]([NH:23][C:24](=[O:34])[C:25]1[C:26]([Cl:33])=[CH:27][C:28]([O:32][CH2:46][CH2:45][CH2:44][NH:43][C:41]([O:40][C:36]([CH3:37])([CH3:39])[CH3:38])=[O:42])=[CH:29][C:30]=1[Cl:31])[CH2:5][C:6]1[CH:7]=[CH:8][C:9]([NH:12][C:13](=[O:22])[C:14]2[C:19]([Cl:20])=[CH:18][CH:17]=[CH:16][C:15]=2[Cl:21])=[CH:10][CH:11]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 4460490tert-butyl N-(3-bromopropyl)carbamateHCID 89719251(S)-3-[4-(2,6-dichlorobenzoylamino)phenyl]-2-(2,6-dichloro-4-hydroxy-benzoylamino)propionic acid methyl ester

Product 1

HCID 89717547(S)-2-[4-(3-tert-butoxycarbonylaminopropoxy)-2,6-dichlorobenzoylamino]-3-[4-(2,6-dichlorobenzoylamino)phenyl]propionic acid methyl esterYield 89%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

To a mixture of (S)-3-[4-(2,6-dichlorobenzoylamino)phenyl]-2-(2,6-dichloro-4-hydroxy-benzoylamino)propionic acid methyl ester (5.05 g, 9.07 mmol), 3-tert-butoxycarbonylaminopropyl bromide (2.59 g, 10.89 mmol), and potassium carbonate (3.77 g, 27.29 mmol) were added DMF (66 mL) and acetone (132 mL) at room temperature. Then, the resulting suspension was heated to reflux for 15 h at which time TLC analysis indicated the absence of starting material. Then, the reaction mixture was cooled to room temperature and diluted with water and the organic compound was extracted into ethyl acetate (2×150 mL). The combined organic layer was washed with brine solution and dried over anhydrous MgSO4. Filtration and concentration gave the crude residue which was purified by ISCO (150 g) column chromatography to obtain 5.75 g (89%) of (S)-2-[4-(3-tert-butoxycarbonylaminopropoxy)-2,6-dichlorobenzoylamino]-3-[4-(2,6-dichlorobenzoylamino)phenyl]propionic acid methyl ester as a white solid. ES(+)-HRMS m/e calcd. for C32H33Cl4N3O7 (M+Na)+ 734.0965, obsd. 734.0961.

Workup

  1. temperatureThen, the resulting suspension was heated
  2. temperatureto reflux for 15 h at which time TLC analysis
  3. extractionthe organic compound was extracted into ethyl acetate (2×150 mL)
  4. washThe combined organic layer was washed with brine solution
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationFiltration and concentration
  7. customgave the crude residue which
  8. customwas purified by ISCO (150 g) column chromatography

Sources & evidence

ORD record
ord-c8829f3b8eaf4a3db1be127acd3eb3b0
Source dataset
uspto-grants-2016_09
Patent number
US09447035B2

Linked notes

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