tert-Butyl bromoacetate → 2-{4-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-7-oxo-[1,4]diazepan-1-yl}-succinic acid 4-tert-butyl ester 1-methyl ester

HRID 2095482Notes

Reaction equation

HRID 2095482 reaction equation
[CH3:1][O:2][C:3](=[O:25])[CH2:4][N:5]1[C:11](=[O:12])[CH2:10][CH2:9][N:8]([C:13](=[O:24])/[CH:14]=[CH:15]/[C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=2)[CH2:7][CH2:6]1.Br[CH2:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29].OS([O-])(=O)=O.[K+]>C1COCC1>[CH3:1][O:2][C:3](=[O:25])[CH:4]([N:5]1[C:11](=[O:12])[CH2:10][CH2:9][N:8]([C:13](=[O:24])/[CH:14]=[CH:15]/[C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=2)[CH2:7][CH2:6]1)[CH2:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29]

Participants

5

Reactant 3

HCID 79177tert-Butyl bromoacetateHCID 516920Potassium bisulfateHCID 67074806{4-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-7-oxo-[1,4]diazepan-1-yl}-acetic acid methyl ester

Product 1

HCID 670742532-{4-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-7-oxo-[1,4]diazepan-1-yl}-succinic acid 4-tert-butyl ester 1-methyl esterYield 18%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

A solution of 0.50 g (1.30 mmol) of {4-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-7-oxo-[1,4]diazepan-1-yl}-acetic acid methyl ester in 25 ml of THF was treated slowly at −78° C. with 1.48 ml (1.48 mmol) of lithium hexamethyldisilylazide 1M in THF. After 30 min at −78° C., a solution of 0.67 ml (4.54 mmol) of tert-butyl bromoacetate in 2.5 ml of THF was added dropwise. The solution was stirred at −78° C. for 5 h, poured on cooled aqueous 10% KHSO4 solution and extracted with Et2O (3×). The organic phases were washed with aqueous 10% NaCl, dried (Na2SO4) and evaporated. The residue was purified on a SiO2-column (n-heptane/EtOAc 1:1 to 2:3) to afford the titled compound in 18% yield as light yellow foam. MS: 499.1 (MH+, 2Cl).

Workup

  1. additionpoured
  2. extractionextracted with Et2O (3×)
  3. washThe organic phases were washed with aqueous 10% NaCl
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. customThe residue was purified on a SiO2-column (n-heptane/EtOAc 1:1 to 2:3)

Sources & evidence

ORD record
ord-9c1a154ce918486eb0f3aae160d9b259
Source dataset
uspto-grants-2013_05
Patent number
US08445674B2

Reaction notes

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