Dimethylformamide → 2-[4-(2-Heptanoylamino-ethyl)-phenylamino]-2-methyl-propionic acid tert-butyl ester

HRID 47829

Reaction equation

HRID 47829 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][NH:10][C:11](=[O:18])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:25]([O:29][C:30](=[O:35])[C:31](Br)([CH3:33])[CH3:32])([CH3:28])([CH3:27])[CH3:26].CN(C)C=O>O>[C:25]([O:29][C:30](=[O:35])[C:31]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][NH:10][C:11](=[O:18])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])=[CH:6][CH:7]=1)([CH3:33])[CH3:32])([CH3:28])([CH3:27])[CH3:26]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 90290tert-Butyl 2-bromo-2-methylpropionateHCID 86586371Heptanoic acid [2-(4-amino-phenyl)-ethyl]-amide

Product 1

HCID 698844682-[4-(2-Heptanoylamino-ethyl)-phenylamino]-2-methyl-propionic acid tert-butyl esterYield 58.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

1H NMR (400 MHz, CDCl3) δ6.94 (d, 2H), 6.61 (d, 2H), 5.35 (s, 1H), 3.57 (s, 2H), 3.43 (m, 2H), 2.66 (t, 3H), 2.07 (t, 2H), 1.55 (m, 3H), 1.24 (m, 5H), 0.84 (t, 3H). A mixture of heptanoic acid [2-(4-amino-phenyl)-ethyl]-amide (1.50 g, 6.04 mmol), cesium carbonate (7.87 g, 24.2 mmol), tert butyl-2-bromoisobutyrate (10.78 g, 48.3 mmol) and dimethylformamide (14.6 mL) was heated at 80° C. for 4 days. The reaction mixture was cooled to ambient temperature, diluted with water and extracted with ether (2×). The combined organics were washed with water and saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure and purified by flash column chromatography (2:3 ethyl acetate/hexanes) to provide 1.37 g (58%) of 2-[4-(2-heptanoylamino-ethyl)-phenylamino]-2-methyl-propionic acid tert-butyl ester as a colorless oil.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. extractionextracted with ether (2×)
  3. washThe combined organics were washed with water and saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. custompurified by flash column chromatography (2:3 ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-cc7b8687c16a426eb76b3fa7fe5fd6a6
Source dataset
uspto-grants-2004_03
Patent number
US06699904B2

Linked notes

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