Ethyl bromoacetate → {4-[(E)-3-(3-Chloro-phenyl)-acryloyl]-7-oxo-[1,4]diazepan-1-yl}-acetic acid ethyl ester

HRID 1867403Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1867403
[Cl:1][C:2]1[CH:3]=[C:4](/[CH:8]=[CH:9]/[C:10]([N:12]2[CH2:18][CH2:17][C:16](=[O:19])[NH:15][CH2:14][CH2:13]2)=[O:11])[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].[CH2:22]([O:24][C:25](=[O:28])[CH2:26]Br)[CH3:23].OS([O-])(=O)=O.[K+]>CN(C=O)C>[CH2:22]([O:24][C:25](=[O:28])[CH2:26][N:15]1[C:16](=[O:19])[CH2:17][CH2:18][N:12]([C:10](=[O:11])/[CH:9]=[CH:8]/[C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[CH2:13][CH2:14]1)[CH3:23]

Komponenten

6

Edukt 4

HCID 7748Ethyl bromoacetate2×HCID 24758Sodium hydride2×HCID 516920Potassium bisulfateHCID 620452481-[(E)-3-(3-Chloro-phenyl)-acryloyl]-[1,4]diazepan-5-one2×

Produkt 1

HCID 68431912{4-[(E)-3-(3-Chloro-phenyl)-acryloyl]-7-oxo-[1,4]diazepan-1-yl}-acetic acid ethyl esterAusbeute 52 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

A solution of 4.33 g (15.53 mmol) of 1-[(E)-3-(3-chloro-phenyl)-acryloyl]-[1,4]diazepan-5-one (intermediate 3A) in 80 ml of DMF was treated at 0° C. with 0.75 g (17.09 mmol) of NaH (55% in oil) in two portions and after 30 min with 1.89 ml (17.09 mmol) of bromo-acetic acid ethyl ester in 1 ml of DMF. The reaction was stirred for 5 h at RT, cooled (0° C.) and treated again with 0.20 g (4.66 mmol) of NaH (55% in oil) and after 20 min with 0.34 ml (3.11 mmol) of bromo-acetic acid ethyl ester. The reaction was warmed up to RT over night, cooled and neutralized with cold aqueous 10% KHSO4 and extracted with Et2O (3×). The organic phases were washed with aqueous saturated NaHCO3, aqueous 10% NaCl, dried over Na2SO4 evaporated and purified by flash silica gel column (EtOAc/n-heptane 1:1 to 9:1) to yield 2.92 g (52%) of the title compound as light yellow viscous oil. MS: 365.0 (MH+, Cl).

Aufarbeitung

  1. temperaturecooled (0° C.)
  2. temperatureThe reaction was warmed up to RT over night
  3. extractionextracted with Et2O (3×)
  4. washThe organic phases were washed with aqueous saturated NaHCO3, aqueous 10% NaCl
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. custompurified by flash silica gel column (EtOAc/n-heptane 1:1 to 9:1)

Quellen und Nachweise

ORD-Eintrag
ord-380dee369dd34b95abc08f71a96a3641
Quelldatensatz
uspto-grants-2009_12
Patentnummer
US07632829B2

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