Sodium hydride → 3-{4-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-7-oxo-[1,4]diazepan-1-yl}-propionic acid ethyl ester

HRID 2095477Notes

Reaction equation

HRID 2095477 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](/[CH:9]=[CH:10]/[C:11]([N:13]2[CH2:19][CH2:18][C:17](=[O:20])[NH:16][CH2:15][CH2:14]2)=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8].Br[CH2:22][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25].[H-].[Na+].OS([O-])(=O)=O.[K+]>CN(C=O)C>[CH2:27]([O:26][C:24](=[O:25])[CH2:23][CH2:22][N:16]1[C:17](=[O:20])[CH2:18][CH2:19][N:13]([C:11](=[O:12])/[CH:10]=[CH:9]/[C:4]2[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=2)[CH2:14][CH2:15]1)[CH3:28]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 68320Ethyl 3-bromopropionateHCID 516920Potassium bisulfateHCID 620449211-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-[1,4]diazepan-5-one

Product 1

HCID 670748533-{4-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-7-oxo-[1,4]diazepan-1-yl}-propionic acid ethyl esterYield 70.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of 4.00 g (12.77 mmol) of 1-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-[1,4]diazepan-5-one and 1.63 ml (12.77 mmol) of ethyl 3-bromopropionate in 60 ml of DMF was treated at 0° C. with 0.61 g (14.05 mmol) of NaH (55% in oil) in two portions. The suspension was stirred after 30 min at RT to get a solution and further stirred over night at 0° C. The reaction was neutralized with cold aqueous 10% KHSO4 and extracted with EtOAc (3×). The organic phases were washed with aqueous 10% NaCl, dried over Na2SO4 evaporated and crystallized (dichloromethane/MeOH) to yield 3.71 g (70%) of the titled compound as an off-white solid. MS: 413.1 (MH+, 2Cl).

Workup

  1. customto get a solution
  2. stirringfurther stirred over night at 0° C
  3. extractionextracted with EtOAc (3×)
  4. washThe organic phases were washed with aqueous 10% NaCl
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customcrystallized (dichloromethane/MeOH)

Sources & evidence

ORD record
ord-397f8431b94646219c29adbcce35a15d
Source dataset
uspto-grants-2013_05
Patent number
US08445674B2

Reaction notes

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